Clinical trial NCT03738241
Conditions: Avian Influenza Influenza Immunisation
Keywords: A/H7N9 Inactivated Influenza Vaccine AS03 Adjuvant Immunogenicity Influenza Phase II Reactogenicity Safety Vaccine
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2018-12-18; Completion date: 2020-06-19
Enrollment: 304 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase II clinical trial in up to 420 males and non-pregnant females, 19 to 70 years of age, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of one dose of a monovalent inactivated split influenza 2017 A/H7N9 virus vaccine (2017 A/H7N9 IIV), administered intramuscularly (IM) at 3.75 mcg hemagglutinin (HA) per dose, given with or without AS03 adjuvant to subjects primed with a monovalent inactivated split influenza 2013 A/H7N9 virus vaccine (2013 A/H7N9 IIV) in DMID Protocols 13-0032 and 13-0033, or to those who are A/H7 IIV-naïve. Phosphate buffered saline (PBS) diluent will be used to achieve the targeted dosage. The study will be conducted at 9 Vaccine and Treatment Evaluation Unit (VTEU) sites (including their subcontractors). Study duration is approximately 17 months with subject participation duration up to 13 months. The primary objectives are: 1) to assess the safety and reactogenicity of 2017 A/H7N9 IIV given with or without AS03 adjuvant following receipt of one dose of study vaccine; 2) to assess the serum hemagglutination inhibition (HAI) and neutralizing (Neut) antibody responses following receipt of the study vaccine.

Detailed description:
This is a Phase II clinical trial in up to 420 males and non-pregnant females, 19 to 70 years of age, inclusive, who are in good health and meet all eligibility criteria, which include a screening erythrocyte sedimentation rate (ESR) laboratory evaluation. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of one dose of a monovalent inactivated split influenza 2017 A/H7N9 virus vaccine (2017 A/H7N9 IIV) manufactured by Sanofi Pasteur (SP), administered intramuscularly (IM) at 3.75 mcg hemagglutinin (HA) per dose, given with or without AS03 adjuvant manufactured by GlaxoSmithKline Biologicals (GSK), to subjects primed with a monovalent inactivated split influenza 2013 A/H7N9 virus vaccine (2013 A/H7N9 IIV) in DMID Protocols 13-0032 and 13-0033, or to those who are A/H7 IIV-naïve. Phosphate buffered saline (PBS) diluent manufactured by Patheon Manufacturing Services LLC will be used to achieve the targeted dosage. Subjects who received the 2013 A/H7N9 IIV in DMID Protocols 13-0032 and 13-0033 or are A/H7 IIV-naïve will be stratified by prior receipt of 2013 A/H7N9 IIV, as well as by site and prior receipt of licensed, seasonal influenza vaccine (defined as receipt of at least one of the 2017-2018 and/or 2018-2019 licensed, seasonal influenza vaccines versus none), then randomly assigned in a 1:1 ratio to 1 of 2 treatment arms to receive 1 dose of 2017 A/H7N9 IIV at 3.75 mcg HA per dose with or without AS03 adjuvant. The study will be conducted at 9 Vaccine and Treatment Evaluation Unit (VTEU) sites (including their subcontractors). Study duration is approximately 17 months with subject participation duration up to 13 months. The primary objectives are: 1) to assess the safety and reactogenicity of 2017 A/H7N9 IIV given with or without AS03 adjuvant following receipt of one dose of study vaccine; 2) to assess the serum hemagglutination inhibition (HAI) and neutralizing (Neut) antibody responses following receipt of the study vaccine. Secondary objectives are: 1) to assess unsolicited non-serious adverse events (AEs) following receipt of the study vaccine; 2) to assess medically-attended adverse events (MAAEs), including new-onset chronic medical conditions (NOCMCs) and potentially immune-mediated medical conditions (PIMMCs), following receipt of the study vaccine; 3) To assess the kinetics and durability of serum HAI and Neut antibody responses following receipt of the study vaccine.

Arms: arm 1: Participants will have prior administration of 2013 A/H7N9 IIV with MF59. Then, 3.75 mcg Hemagglutinin (HA) per 0.5 ml dose of 2017 A/H7N9 Inactivated Influenza Virus Vaccine (IIV) + AS03 adjuvant administered intramuscularly on Day 1 (n=50) or 3.75 mcg HA per 0.5 ml dose of 2017 A/H7N9 IIV unadjuvanted administered intramuscularly on Day 1 (n=50). Phosphate buffered saline (PBS) diluent may be used to achieve targeted dosages. arm 2: Participants will have prior administration of 2013 A/H7N9 IIV with AS03. Then, 3.75 mcg Hemagglutinin (HA) per 0.5 ml dose of 2017 A/H7N9 Inactivated Influenza Virus Vaccine (IIV) + AS03 adjuvant administered intramuscularly on Day 1 (n=50) or 3.75 mcg HA per 0.5 ml dose of 2017 A/H7N9 IIV unadjuvanted administered intramuscularly on Day 1 (n=50). Phosphate buffered saline (PBS) diluent may be used to achieve targeted dosages. arm 3: Participants will have prior administration of 2013 A/H7N9 IIV 15 mcg or 45 mcg unadjuvanted. Then, 3.75 mcg Hemagglutinin (HA) per 0.5 ml dose of 2017 A/H7N9 Inactivated Influenza Virus Vaccine (IIV) + AS03 adjuvant administered intramuscularly on Day 1 (n=50) or 3.75 mcg HA per 0.5 ml dose of 2017 A/H7N9 IIV unadjuvanted administered intramuscularly on Day 1 (n=50). Phosphate buffered saline (PBS) diluent may be used to achieve targeted dosages. arm 4: Participants will have prior administration of 2013 A/H7N9 IIV + MF59 or AS03 (1st) then 2013 A/H7N9 IIV 15 mcg (2nd). Then, 3.75 mcg Hemagglutinin (HA) per 0.5 ml dose of 2017 A/H7N9 Inactivated Influenza Virus Vaccine (IIV) + AS03 adjuvant administered intramuscularly on Day 1 (n=30) or 3.75 mcg HA per 0.5 ml dose of 2017 A/H7N9 IIV unadjuvanted administered intramuscularly on Day 1 (n=30). Phosphate buffered saline (PBS) diluent may be used to achieve targeted dosages. arm 5: Participants who are A/H7 IIV-Naïve. Then, 3.75 mcg Hemagglutinin (HA) per 0.5 ml dose of 2017 A/H7N9 Inactivated Influenza Virus Vaccine (IIV) + AS03 adjuvant administered intramuscularly on Day 1 (n=30) or 3.75 mcg HA per 0.5 ml dose of 2017 A/H7N9 IIV unadjuvanted administered intramuscularly on Day 1 (n=30). Phosphate buffered saline (PBS) diluent may be used to achieve targeted dosages.
Interventions: intervention 1: A/H7N9 intervention 2: AS03 intervention 3: Phosphate Buffered Saline (PBS) diluent
Intervention descriptions: intervention 1: Monovalent split 2017 A/H7N9 Inactivated Influenza Virus Vaccine containing the Hemagglutinin (HA) and Neuraminidase (NA) from low pathogenic avian influenza A/Hong Kong/125/2017 (H7N9) and the PB2, PB1, PA, NP, M and NS from A/Puerto Rico/8/1934 (H1N1). The HA content of the 2017 A/H7N9 vaccine formulations were determined by Single Radial Immunodiffusion (SRID) assay to be approximately two times higher (14.45 mcg of HA per 0.5 mL dose) than the targeted HA content on the label (7.5 mcg of HA per 0.5 mL dose). intervention 2: AS03 oil-in-water emulsion-based adjuvant system containing DL-alpha-tocopherol, squalene, polysorbate 80, and a buffer. intervention 3: 0.006M PBS diluent for Influenza Virus Vaccine.

Protocol documents:
Prot_000.pdf: 
 
A Phase II Study to Assess the Safety, Reactogenicity and Immunogenicity of a 
Single Dose of 2017 A/H7N9 Inactivated Influenza Vaccine (IIV) Administered 
Intramuscularly with or without AS03 Adjuvant in 2013 A/H7N9 IIV Primed or 
A/H7 IIV Naïve Subjects 
 
DMID Protocol Number: 17-0090 
 
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: Hana El Sahly, MD, FIDSA 
DMID Clinical Project Manager: Wendy Buchanan, RN, MS 
DMID Medical Monitor: Mohamed Elsafy, MD 
DMID Medical Officer: Francisco Leyva, MD, PhD, ScM 
DMID Scientific Lead: Chris Roberts, PhD 
 
Version: 3.0 
18 December 2019 


DMID Protocol 17-0090 
Version 3.0 
2017 H7N9 Revaccination 
18 December 2019 
 
i 
STATEMENT OF COMPLIANCE 
This trial will be carried out in accordance with Good Clinical Practice (GCP) as required by the 
following: 
• 
United States (US) 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 Council for Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use E6(R2) Good Clinical Practice (ICH E6 GCP): 
Integrated Addendum to ICH E6(R1) Guidance for Industry, published in the Federal 
Register (83 Federal Register 8882 (2018)), including the latest finalized revision 
• 
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 17-0090 
Version 3.0 
2017 H7N9 Revaccination 
18 December 2019 
 
ii 
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 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 Institutional Review Board 
(IRB)/Institutional Ethics Committee (IEC) approval, except when necessary to protect the 
safety, rights or welfare of subjects. 
Site Principal Investigator: 
 
Signed: 
 
 
Date: 
 
 
Name 
Title 
 
 
 
 


DMID Protocol 17-0090 
Version 3.0 
2017 H7N9 Revaccination 
18 December 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 ................................................................................................................................1 
2 
Background Information and Scientific Rationale .................................................................3 
2.1 
Background Information .............................................................................................3 
2.1.1 Public Readiness and Emergency Preparedness Act ......................................6 
2.2 
Scientific Rationale .....................................................................................................7 
2.3 
Potential Risks and Benefits .......................................................................................9 
2.3.1 Potential Risks ................................................................................................9 
2.3.2 Known Potential Benefits .............................................................................16 
3 
Study Objectives and Outcome Measures ............................................................................17 
3.1 
Study Objectives .......................................................................................................17 
3.1.1 Primary Objectives........................................................................................17 
3.1.2 Secondary Objectives....................................................................................17 
3.1.3 Exploratory Objectives .................................................................................17 
3.2 
Study Outcome Measures .........................................................................................18 
3.2.1 Primary Outcome Measures ..........................................................................18 
3.2.2 Secondary Outcome Measures ......................................................................19 
3.2.3 Exploratory Outcome Measures ...................................................................19 
4 
Study Design .........................................................................................................................21 
5 
Study Enrollment and Withdrawal........................................................................................23 
5.1 
Eligibility Criteria .....................................................................................................23 
5.1.1 Subject Inclusion Criteria .............................................................................23 
5.1.2 Subject Exclusion Criteria ............................................................................25 
5.2 
Treatment Assignment Procedures ...........................................................................27 
5.2.1 Enrollment and Randomization Procedures..................................................27 
5.2.2 Masking Procedures ......................................................................................28 
5.2.3 Reasons for Withdrawals and Discontinuation of Study Product 
Administration ..............................................................................................28 
5.2.4 Handling of Withdrawals and Discontinuation of Study Product 
Administration ..............................................................................................29 
5.2.5 Subject Replacement .....................................................................................30 


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5.2.6 Termination of Study ....................................................................................30 
6 
Study Intervention/Investigational Product ..........................................................................31 
6.1 
Study Product Description ........................................................................................31 
6.1.1 Acquisition ....................................................................................................31 
6.1.2 Formulation, Storage, Packaging, and Labeling ...........................................32 
6.1.3 Study Product Storage and Stability Procedures ..........................................33 
6.2 
Dosage, Preparation and Administration of Study Intervention/Investigational 
Product ......................................................................................................................34 
6.3 
Modification of Study Intervention/Investigational Product for a Subject ...............35 
6.4 
Accountability Procedures for the Study Intervention/Investigational Product .......36 
6.5 
Assessment of Subject Compliance with Study Intervention/Investigational Product
...................................................................................................................................36 
6.6 
Concomitant Medications/Treatments ......................................................................37 
7 
Study Procedures/Evaluations ..............................................................................................38 
7.1 
Clinical Evaluations ..................................................................................................38 
7.2 
Laboratory Evaluations .............................................................................................39 
7.2.1 Clinical Laboratory Evaluations ...................................................................39 
7.2.2 Special Assays or Procedures .......................................................................40 
7.2.3 Specimen Preparation, Handling and Shipping ............................................43 
8 
Study Schedule......................................................................................................................44 
8.1 
Screening (Optional) and Enrollment Visits .............................................................44 
8.1.1 Visit 00, Screening (Day -28 to -1), Clinic Visit, Optional ..........................44 
8.1.2 Visit 01, Day 1, Enrollment (for subjects previously screened at Day -28 to -
1) and Study Vaccination, Clinic Visit .........................................................45 
8.1.3 Visit 01, Day 1, Enrollment/Baseline (for subjects not previously screened 
at Day -28 to -1) and Study Vaccination, Clinic Visit ..................................47 
8.2 
Follow-up Visits........................................................................................................49 
8.2.1 Visit 02, Day 2, Clinic Visit..........................................................................49 
8.2.2 Visit 03, Day 4, Clinic Visit..........................................................................50 
8.2.3 Visit 04, Day 8, Clinic Visit..........................................................................51 
8.2.4 Visit 05, Day 15, Clinic Visit........................................................................52 
8.2.5 Visit 06, Day 22, Clinic Visit........................................................................53 
8.2.6 Visit 07, Day 61, Safety Follow-up, Phone Call...........................................53 
8.2.7 Visit 08, Day 91, Clinic Visit........................................................................53 
8.2.8 Visit 09, Day 121, Safety Follow-up, Phone Call.........................................54 
8.2.9 Visit 10, Day 181, Clinic Visit......................................................................54 
8.3 
Final Visit..................................................................................................................55 
8.3.1 Visit 11, Day 366, Safety Follow-up, Phone Call.........................................55 
8.4 
Early Termination Visit (if needed) ..........................................................................55 
8.5 
Unscheduled Visit (if needed) ..................................................................................56 


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9 
Assessment of Safety ............................................................................................................58 
9.1 
Specification of Safety Parameters ...........................................................................58 
9.2 
Methods and Timing for Assessing, Recording and Analyzing Safety Parameters .58 
9.2.1 Adverse Events .............................................................................................58 
9.2.2 Reactogenicity...............................................................................................60 
9.2.3 Additional Adverse Event Severity Grading ................................................62 
9.2.4 Serious Adverse Events ................................................................................64 
9.2.5 Procedures to be Followed in the Event of Abnormal Laboratory Test 
Values or Abnormal Clinical Findings .........................................................65 
9.3 
Reporting Procedures ................................................................................................65 
9.3.1 Serious Adverse Events ................................................................................65 
9.3.2 Regulatory Reporting for Studies Conducted Under DMID-Sponsored IND
.......................................................................................................................66 
9.3.3 Reporting of Pregnancy ................................................................................67 
9.4 
Type and Duration of Follow-up of Subjects after Adverse Events .........................67 
9.5 
Halting Rules ............................................................................................................67 
9.6 
Safety Oversight........................................................................................................69 
9.6.1 Independent Safety Monitor (ISM) ...............................................................69 
9.6.2 Data and Safety Monitoring Board (DSMB) ................................................70 
10 
Clinical Monitoring ...............................................................................................................72 
10.1 
Site Monitoring Plan .................................................................................................72 
11 
Statistical Considerations ......................................................................................................73 
11.1 
Introduction ...............................................................................................................73 
11.2 
Study Hypotheses......................................................................................................73 
11.3 
Study Outcome Measures .........................................................................................73 
11.4 
Sample Size Considerations ......................................................................................73 
11.4.1 Study Population ...........................................................................................73 
11.4.2 Subject Enrollment and Follow-up ...............................................................74 
11.4.3 Sample Size ...................................................................................................74 
11.5 
Planned Interim Analyses .........................................................................................81 
11.5.1 Interim Safety Review ..................................................................................81 
11.5.2 Interim Immunogenicity Review ..................................................................82 
11.6 
Final Analysis Plan ...................................................................................................82 
11.6.1 Analysis Populations .....................................................................................83 
11.6.2 Safety Data ....................................................................................................83 
11.6.3 Immunogenicity Data....................................................................................84 
11.6.4 Missing Values and Outliers .........................................................................85 
12 
Data Collection Forms and Access to Source Data/Documents ...........................................86 
13 
Quality Control and Quality Assurance ................................................................................87 
14 
Ethics/Protection of Human Subjects ...................................................................................88 


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14.1 
Ethical Standard ........................................................................................................88 
14.2 
Institutional Review Board (IRB) .............................................................................88 
14.3 
Informed Consent Process ........................................................................................88 
14.4 
Exclusion of Women, Minorities and Children (Special Populations) .....................90 
14.5 
Subject Confidentiality .............................................................................................91 
14.6 
Study Discontinuation ...............................................................................................92 
14.7 
Costs, Subject Compensation and Research Related Injuries ...................................93 
14.8 
Future Use of Stored Specimens ...............................................................................93 
15 
Data Handling and Record Keeping .....................................................................................96 
15.1 
Data Management Responsibilities...........................................................................96 
15.2 
Data Capture Methods ..............................................................................................96 
15.3 
Types of Data ............................................................................................................97 
15.4 
Timing/Reports .........................................................................................................97 
15.5 
Study Records Retention...........................................................................................98 
15.6 
Protocol Deviations ...................................................................................................98 
16 
Publication Policy .................................................................................................................99 
17 
Literature References ..........................................................................................................100 
Appendices ...................................................................................................................................105 
Appendix A. 
SCHEDULE OF STUDY PROCEDURES AND EVALUATIONS .........106 
Appendix B. 
LIST OF POTENTIALLY IMMUNE-MEDIATED MEDICAL 
CONDITIONS (PIMMCs)..................................................................................................109 
 
 
 
 


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LIST OF TABLES 
Table 1: Study Design .................................................................................................................. xix 
 
Table 3: Venipuncture Volumes ....................................................................................................42 
Table 4: Injection Site Reactogenicity Grading .............................................................................61 
Table 5: Injection Site Reactogenicity Measurements ...................................................................61 
Table 6: Subjective Systemic Reactogenicity Grading ..................................................................62 
Table 7: Quantitative Systemic (Oral Temperature) Reactogenicity Grading ...............................62 
Table 8: Pulse and BP Adverse Event Grading .............................................................................63 
Table 9: Clinical Safety Laboratory Adverse Event Grading ........................................................63 
Table 10: Previously Primed Subjects For Potential Enrollment in 17-0090 ................................75 
Table 11: Power (%) to Detect Safety Events ...............................................................................77 
Table 12: Precision of Binomial Confidence Intervals ..................................................................79 
Table 13: Minimum Detectable Difference in Proportion Responders .........................................79 
Table 14: Vaccination Period.......................................................................................................106 
Table 15: Early Termination and Unscheduled Visits .................................................................108 
 
 
 


DMID Protocol 17-0090 
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LIST OF FIGURES 
Figure 1: Schematic of Study Design ............................................................................................xx 
 


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ix 
LIST OF ABBREVIATIONS 
A/H1N1 
Influenza A Virus of the H1N1 Subtype 
A/H1N2v 
Influenza A Virus of the H1N2 Variant 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/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 
AE 
Adverse Event/Adverse Experience 
AESIs 
Adverse Events of Special Interest 
ALT 
Alanine Aminotransferase 
ANCA 
Anti-Neutrophil Cytoplasmic Antibody 
AS03 
Adjuvant System (03) 
BARDA 
Biomedical Advanced Research and Development Authority 
BLA 
Biologics License Application 
BMI 
Body Mass Index 
BP 
Blood Pressure 
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 
COI 
Conflict of Interest 
Cr 
Creatinine 
CROMS 
Clinical Research Operations and Management Support 
CSL 
Commonwealth Serum Laboratories 
CSR 
Clinical Study Report 
°C 
Degrees Celsius 
°F 
Degrees Fahrenheit 
D 
Day(s) 
DCF 
Data Collection Form 
DHHS 
Department of Health and Human Services 
DMID 
Division of Microbiology and Infectious Diseases, NIAID, NIH 


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DSMB 
Data and Safety Monitoring Board 
eCRF 
Electronic Case Report Form 
EDCSM 
Electronic Data Capture System 
ELISA 
Enzyme-Linked Immunosorbent Assay 
ELLA 
Enzyme-Linked Lectin Assay 
ESR 
Erythrocyte Sedimentation Rate 
FDA 
Food and Drug Administration 
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 
HRSA 
Health Resources and Services Administration 
IATA 
International Air Transport Association 
ICD-10 
10th revision of the International Statistical Classification of 
Diseases and Related Health Problems 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
ICMJE 
International Committee of Medical Journal Editors 
IEC 
Institutional Ethics Committee 
IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
IIV 
Inactivated Influenza Virus Vaccine 
IIV3 
Trivalent IIV 
IM 
Intramuscular(ly) 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
IU/L 
International Unit(s) per Liter 
LLC 
Limited Liability Company 
MAAE 
Medically-Attended Adverse Event 


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mcg 
Microgram(s) 
µL 
Microliter(s) 
MedDRA 
Medical Dictionary for Regulatory Activities 
MF59 
MF59C.1 Adjuvant 
mg/dL 
Milligram(s) per Deciliter 
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 
NAI 
Neuraminidase Inhibiting or Inhibition 
Neut 
Neutralizing or Neutralization 
NIAID 
National Institute of Allergy and Infectious Diseases, NIH 
NIH 
National Institutes of Health, DHHS 
NSAIDs 
Non-Steroidal Anti-Inflammatory Drugs 
NOCMCs 
New-Onset Chronic Medical Conditions 
OER 
Office of Extramural Research 
OHRP 
Office for Human Research Protections 
PBMC 
Peripheral Blood Mononuclear Cell 
PBS 
Phosphate Buffered Saline 
pH1N1 
2009 H1N1 Influenza 
PHI 
Personal Health Information 
PI 
Principal Investigator 
PIMMCs 
Potentially Immune-Mediated Medical Conditions 
PLT 
Platelets 
PP 
Per Protocol 
PREP Act 
Public Readiness and Emergency Preparedness Act 
PRN 
As Needed 
PT 
Preferred Term 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SAP 
Statistical Analysis Plan 
SDCC 
Statistical and Data Coordinating Center 
SMA 
Secondary Medical Assessor 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 


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SP 
Sanofi Pasteur 
SRID 
Single Radial Immunodiffusion 
TBD 
To Be Determined 
T. Bili 
Total Bilirubin 
US 
United States 
V 
Visit(s) 
VTEU 
Vaccine and Treatment Evaluation Unit 
WBC 
White Blood Cells 
WHO 
World Health Organization 
 


DMID Protocol 17-0090 
Version 3.0 
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18 December 2019 
 
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PROTOCOL SUMMARY 
Title: 
A Phase II Study to Assess the Safety, Reactogenicity and 
Immunogenicity of a Single Dose of 2017 A/H7N9 Inactivated 
Influenza Vaccine (IIV) Administered Intramuscularly with or 
without AS03 Adjuvant in 2013 A/H7N9 IIV Primed or A/H7 IIV 
Naïve Subjects 
Phase: 
II 
Population: 
Up to 420 males and non-pregnant females, 19 to 70 years of age, 
inclusive, who are in good health and meet all eligibility criteria 
Number of Sites: 
9 Vaccine and Treatment Evaluation Unit (VTEU) sites (including 
their subcontractors) 
Study Duration: 
Approximately 17 months 
Subject Participation 
Duration: 
Up to 13 months 
Estimated Time to Complete 
Enrollment: 
Approximately 16 weeks 
Description of Agent: 
• Monovalent inactivated split influenza A/H7N9/Hong 
Kong/125/2017 virus vaccine (2017 A/H7N9 IIV) 
manufactured by Sanofi Pasteur (SP) 
• AS03 adjuvant manufactured by GlaxoSmithKline 
Biologicals (GSK) 
• Phosphate buffered saline (PBS) diluent manufactured by 
Patheon Manufacturing Services LLC 
Study Objectives: 
 
Primary: 
Safety: 
• To assess the safety and reactogenicity of 2017 A/H7N9 
IIV given with or without AS03 adjuvant following receipt 
of one dose of study vaccine. 
 


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xiv 
Immunogenicity: 
• To assess the serum hemagglutination inhibition (HAI) and 
neutralizing (Neut) antibody responses following receipt of 
the study vaccine. 
Secondary: 
Safety: 
• To assess unsolicited non-serious adverse events (AEs) 
following receipt of the study vaccine. 
• To assess medically-attended adverse events (MAAEs), 
including new-onset chronic medical conditions 
(NOCMCs) and potentially immune-mediated medical 
conditions (PIMMCs), following receipt of the study 
vaccine. 
Immunogenicity: 
• To assess the kinetics and durability of serum HAI and 
Neut antibody responses following receipt of the study 
vaccine. 
Exploratory: 
Immunogenicity: 
• To assess the effects of age, sex, body mass index (BMI), 
and prior receipt of seasonal or non-study pandemic 
influenza vaccine(s) on serum HAI and Neut antibody 
responses following receipt of the study vaccine. 
• To determine, in at least a subset of samples, the serum 
antibody responses to N9 NA. 
• To assess, in at least a subset of samples, HA stem-specific 
antibody responses. 
• 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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Study Outcome Measures: 
 
Primary: 
Safety: 
• Occurrence of all serious adverse events (SAEs) from the 
time of study vaccination through approximately 12 
months after study vaccination. 
• Occurrence of solicited injection site and systemic 
reactogenicity events from the time of study vaccination 
through 7 days after study vaccination. 
• Occurrence of clinical safety laboratory AEs from the time 
of study vaccination through approximately 7 days after 
study vaccination. 
Immunogenicity: 
• For HAI and Neut antibodies, percentage of subjects 
achieving seroconversion against the 2017 influenza 
A/H7N9 study vaccine virus (defined as either a pre-
vaccination titer <10 and a post-vaccination titer ≥1:40 or a 
pre-vaccination titer ≥10 and a minimum four-fold rise in 
post-vaccination antibody titer) approximately 21 days 
after study vaccination. 
• For HAI and Neut antibodies, percentage of subjects 
achieving titer ≥40 against the 2017 influenza A/H7N9 
study vaccine virus approximately 21 days after study 
vaccination. 
• Geometric mean titers (GMTs) of serum HAI and Neut 
antibodies against the 2017 influenza A/H7N9 study 
vaccine virus approximately 21 days after study 
vaccination. 
Secondary: 
Safety: 
• Occurrence of all unsolicited non-serious AEs from the 
time of study vaccination through approximately 21 days 
after study vaccination. 


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• Occurrence of all MAAEs, including NOCMCs and 
PIMMCs, from the time of study vaccination through 
approximately 12 months after study vaccination. 
Immunogenicity: 
• For HAI and Neut antibodies, percentage of subjects 
seroconverting against the 2017 influenza A/H7N9 study 
vaccine virus approximately 7 and 180 days after study 
vaccination. 
• For HAI and Neut antibodies, percentage of subjects 
achieving a titer ≥40 against the 2017 influenza A/H7N9 
study vaccine virus approximately 7 and 180 days after 
study vaccination. 
• GMTs of serum HAI and Neut antibodies against the 2017 
influenza A/H7N9 study vaccine virus approximately 7 
and 180 days after study vaccination. 
• The percentage of subjects seroconverting, the percentage 
of subjects achieving a titer ≥40, and the GMTs of serum 
HAI and Neut antibodies against the 2013 influenza 
A/H7N9 vaccine virus (priming vaccine virus) 
approximately 21 days after study vaccination. 
Exploratory: 
Immunogenicity: 
• For HAI and Neut antibodies, GMTs and percentage of 
subjects seroconverting against the 2017 influenza 
A/H7N9 study vaccine virus approximately 21 days after 
study vaccination, by age, sex, BMI, the inclusion of an 
adjuvant in the prime and/or boost regimens, and prior 
receipt of seasonal or non-study pandemic influenza 
vaccine(s). 
• GMTs and percentage of subjects seroconverting (defined 
as four-fold change from baseline) of serum anti-NA (by 
enzyme-linked immunosorbent assay [ELISA]) or anti-
neuraminidase inhibition (NAI) (by enzyme-linked lectin 
assay [ELLA]) antibodies immediately prior to and 7, 21 
and 180 days after study vaccination. 


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• Correlation between the inclusion of an adjuvant in the 
prime and/or boost regimens with the elicited H7 HA and 
N9 NA-specific serum antibody titers approximately 21 
days after study vaccination. 
• GMTs of HA stem-specific antibody immediately prior to 
and approximately 7, 21 and 180 days after study 
vaccination. 
• For HAI and Neut antibodies, GMTs and percentage of 
subjects seroconverting against antigenically drifted 
variants of influenza A/H7 viruses approximately 21 days 
after study vaccination. 
 
Description of Study Design: This is a Phase II clinical trial in up to 420 males and non-
pregnant females, 19 to 70 years of age, inclusive, who are in good 
health and meet all eligibility criteria, which include a screening 
erythrocyte sedimentation rate (ESR) laboratory evaluation. This 
clinical trial is designed to assess the safety, reactogenicity and 
immunogenicity of one dose of a monovalent inactivated split 
influenza 2017 A/H7N9 virus vaccine (2017 A/H7N9 IIV) 
manufactured by Sanofi Pasteur (SP), administered 
intramuscularly (IM) at 3.75 mcg hemagglutinin (HA) per dose, 
given with or without AS03 adjuvant manufactured by 
GlaxoSmithKline Biologicals (GSK), to subjects primed with a 
monovalent inactivated split influenza 2013 A/H7N9 virus vaccine 
(2013 A/H7N9 IIV) in DMID Protocols 13-0032 and 13-0033, or 
to those who are A/H7 IIV-naïve. Phosphate buffered saline (PBS) 
diluent manufactured by Patheon Manufacturing Services LLC 
will be used to achieve the targeted dosage. 
Subjects who received the 2013 A/H7N9 IIV in DMID Protocols 
13-0032 and 13-0033 or are A/H7 IIV-naïve will be stratified by 
prior receipt of 2013 A/H7N9 IIV, as well as by site and prior 
receipt of licensed, seasonal influenza vaccine (defined as receipt 
of at least one of the 2017-2018 and/or 2018-2019 licensed, 
seasonal influenza vaccines versus none), then randomly assigned 
in a 1:1 ratio to 1 of 2 treatment arms to receive 1 dose of 2017 
A/H7N9 IIV at 3.75 mcg HA per dose with or without AS03 
adjuvant (see Table 1). 


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Reactogenicity will be measured by the occurrence of solicited 
injection site and systemic reactions from the time of study 
vaccination through 7 days after study vaccination. Unsolicited 
non-serious adverse events (AEs) will be collected from the time 
of study vaccination through approximately 21 days after study 
vaccination. Serious adverse events (SAEs) and medically-
attended adverse events (MAAEs), including new-onset chronic 
medical conditions (NOCMCs) and potentially immune-mediated 
medical conditions (PIMMCs), will be collected from the time of 
study vaccination through approximately 12 months after study 
vaccination. Clinical safety laboratory evaluations (hematology 
and chemistry) will be performed on venous blood collected 
immediately prior to study vaccination and approximately 7 days 
after study vaccination. 
Immunogenicity testing will include performing serological assays 
to assess hemagglutination inhibition (HAI), neutralizing (Neut), 
neuraminidase inhibition (NAI), neuraminidase (NA)-specific, and 
HA stem-specific antibody titers at multiple time points following 
each study vaccination. Venous blood will also be collected at 
multiple time points following study vaccination for the future 
research use of serum, plasma and peripheral blood mononuclear 
cells (PBMCs). 
Correlation of the H7 HA and N9 NA-specific serum antibody 
responses to the inclusion of an adjuvant in the prime and/or boost 
regimens will also be determined. 
 






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1 
KEY ROLES 
Lead Principal Investigator: 
 
Hana El Sahly, MD 
Baylor College of Medicine 
 
DMID Clinical Project Manager: 
Wendy Buchanan, RN, 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 Leyva, MD, PhD, ScM 
Division of Microbiology and Infectious Diseases 
NIAID, NIH 
 
DMID Scientific Lead: 
 
Chris Roberts, PhD 
Division of Microbiology and Infectious Diseases 
NIAID, NIH 
 
Site Principal Investigators: 
Hana El Sahly, MD 
Baylor College of Medicine 
 
Inci Yildirim, MD 
Emory University School of Medicine and Emory Children’s 
Center 
 
Varun Phadke, MD 
The Hope Clinic of Emory Vaccine Center 
 
Sharon Frey, MD 
Saint Louis University 
 
Pat Winokur, MD 
University of Iowa Hospitals and Clinics 
 
Lisa Jackson 
Kaiser Permanente Washington Health Research Institute 


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David Bernstein, MD, MA 
Cincinnati Children’s Hospital Medical Center 
 
C. Buddy Creech, MD, MPH 
Vanderbilt University Medical Center 
 
Wilbur Chen, MD 
University of Maryland, Baltimore 
 
Richard Rupp, MD 
University of Texas Medical Branch, Galveston 
 
Safety and Pharmacovigilance: 
 
DMID Pharmacovigilance Group 
Clinical Research Operations and Management Support 
(CROMS) 
 
Statistical and Data Coordinating 
Center: 
The Emmes Company, LLC 
 
Clinical Materials Services: 
Fisher BioServices 
 
Central (Clinical) Laboratory: 
PPD Global Central Laboratories 
 
HAI and Neut Antibody Assays 
Laboratory: 
Southern Research 
 
Additional Serological Assays 
Laboratories: 
To Be Determined (TBD) 
 
 
 


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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, 
H5N6, H3N2v, H1N2v, H7N7, H9N2, 2009 H1N1, and most recently H7N9, underscores the 
need for focused efforts to prepare for the next influenza pandemic [1-9]. 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 [10]. Excess mortality, high 
morbidity and social disruption were all noted during the 1957 influenza A/H2N2 and the 1968 
influenza A/H3N2 pandemics [11]. 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 [12, 13]. 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 [14]. 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 (NAI) antibodies in protection against disease [15]. In a recent human influenza 


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challenge study, serum NAI antibody levels were also identified as an independent correlate of 
protection against influenza illness [16]. In the current study, the correlation of the inclusion of 
an adjuvant in the prime and/or boost regimens with the elicited humoral antibody responses to 
the H7 HA and N9 NA will be determined. 
Several approaches have been used to increase the immunogenicity of IIVs. Standard-dose 
seasonal IIVs contain 7.5 to 15 mcg of HA antigen per seasonal influenza vaccine strain for 
children and adults up to 64 years of age. 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 [17-25]. Higher HA dosage influenza vaccines can lead to 
enhanced antibody responses in the elderly [26]. In 2009, a high-dose seasonal IIV containing 4 
times the standard HA antigen per seasonal influenza 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, 2013 A/H7N9) 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 [27, 28]. Due to the poor immunogenicity of A/H5 and 
A/H7 vaccines, the inclusion of adjuvants was evaluated to assess their ability to boost anti-viral 
serum IgG levels. In the US, 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 [29-31]. In contrast, the use of oil-in-water emulsion adjuvants, most 
notably proprietary adjuvants AS03 and MF59 produced by GSK and Novartis (now Seqirus), 
respectively, has resulted in increased antibody responses to IIVs containing novel HAs in 
numerous clinical trials [32-36]. 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 subjects who received the adjuvanted formulations [34]. 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 treatment arms only the 30 mcg formulation met the CHMP criterion for 
seroconversion [34]. GSK received approval for the registration of a pre-pandemic AS03-
adjuvanted, monovalent inactivated influenza 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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influenza 2009 A/H1N1 virus vaccine (Pandemrix™) and Novartis’ egg-derived MF59-
adjuvanted, monovalent 2009 A/H1N1 IIV (FOCETRIATM). These adjuvanted monovalent 2009 
A/H1N1 IIVs 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 [29]. 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 [37-45]. See Section 
2.3.1 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 [46-51]. In response to emerging influenza A/H5N8 viruses that 
have caused extensive outbreaks in domestic poultry and wild birds in South East Asia [52, 53], 
NIAID is also conducting two ongoing clinical trials with an A/H5N8 vaccine produced by 
bioCSL (now Seqirus) administered with either AS03 (GSK) or MF59 (Seqirus) adjuvants in 
healthy subjects, 19 to 64 years of age (DMID Protocol 15-0064; NCT02624219 and DMID 
Protocol 15-0066; NCT03014310). 
Since March of 2013 [54], 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. China 
is currently experiencing it’s “sixth wave” of A/H7N9 infections, and as of March 2, 2018, a 
total of 1,567 laboratory-confirmed human infections with avian influenza A/H7N9 viruses have 
been reported by the World Health Organization [55]. 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 [56]. 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 


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to human, with most isolates appearing to have retained their susceptibility to NA inhibitors [56]. 
Laboratory studies have shown that influenza A/H7N9 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 [57, 58]. 
During the “fifth wave” of outbreaks which began in October 2016, more human cases of 
A/H7N9 infection were reported in China than during any prior A/H7N9 epidemic wave [55]. In 
addition, an antigenically distinct lineage of these fifth wave influenza A/H7N9 viruses known as 
the Yangtze River Delta lineage has recently emerged and has been associated with an increasing 
number of human cases [59]. 
The US Department of Health and Human Services (DHHS) recently determined influenza 
A/H7N9 virus as having a significant potential to cause a pandemic, and the greatest risk of 
causing severe disease. As a result, DHHS has supported the production of fifth wave pre-
pandemic A/H7N9 IIVs for the US stockpile and for an assessment of safety and 
immunogenicity in clinical trials. 
2.1.1 Public Readiness and Emergency Preparedness Act 
For this protocol, the study products (2017 A/H7N9 IIV manufactured by Sanofi Pasteur and 
AS03 adjuvant 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 A/H7N9 IIV with or without AS03 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. 
An individual who suffers a serious physical injury or death from administration and use of the 
2017 A/H7N9 IIV with or without AS03 adjuvant may request benefits from the CICP. A serious 


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physical injury means an injury that is life-threatening, or 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, and the Department of 
Veterans Affairs or Workers’ Compensation programs do not 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 US 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)/DHHS, 
produced several novel pre-pandemic vaccines that were or are currently being 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 “mix and match” clinical trials have demonstrated that 
adjuvant use results in a significant dose-sparing effect. 
The large number of human infections starting with the “fifth wave” of outbreaks in late 2016 
has increased the pandemic risk potential of influenza A/H7N9 viruses circulating in China. The 
Yangtze River Delta lineage, a distinct A/H7N9 viral lineage, has now emerged and has been 
associated with many of the fifth wave cases. Fifth wave A/H7N9 viruses have led to a broader 
geographic spread of infected birds and human cases within China than previously reported. 
Further, several influenza A/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 [56, 59]. To date, no cases of 
A/H7N9 from the new viral 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 influenza A/H7N9 viruses 
and serological studies indicate that the stockpiled 2013 A/H7N9 IIV manufactured several years 


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ago does not induce protective HAI or Neut antibodies against the Yangtze River Delta lineage. 
Hence, there is broad consensus across DHHS and interagency leadership that a new vaccine 
should be developed that would be effective against the currently predominating influenza 
A/H7N9 viruses. 
Several candidate vaccine viruses are under evaluation by the Centers for Disease Control and 
Prevention (CDC) and the World Health Organization (WHO) H5 Reference Laboratories 
Network. Under contract to BARDA/DHHS, Sanofi Pasteur has produced monovalent 
inactivated split influenza 2017 A/H7N9 virus vaccine (2017 A/H7N9 IIV) using largely the 
same manufacturing process as its licensed, seasonal trivalent IIV (IIV3). 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 Pasteur 2017 A/H7N9 IIV with 
the GSK AS03 adjuvant. See Sections 2.3.1 and 6.1 for additional details on the 2017 A/H7N9 
IIV. 
Heterologous prime-boost vaccination regimens have shown considerable promise in expanding 
the breadth and durability of cross-clade antibody responses [60, 61]. In addition, the use of 
adjuvants and extending the interval between the priming (first) and boosting (second) doses of 
vaccine have also led to more robust cross-clade antibody responses [60-63]. 
The goal of this clinical trial is to assess the safety, reactogenicity and immunogenicity of a 
single boosting dose of 2017 A/H7N9 IIV administered IM at the 3.75 mcg of hemagglutinin 
(HA) dosage when given with or without AS03 adjuvant to subjects who have received 2013 
A/H7N9 IIV in 2013-2014, and in A/H7 IIV-naïve subjects who are 19 to 70 years of age, 
inclusive. The safety, reactogenicity and adjuvant effect of the study vaccine in primed 
individuals, as well as the priming effects of different A/H7N9 IIV regimens (with/without AS03 
vs MF59) will be assessed. Another goal of this study is to assess whether serum 
immunoglobulin elicited by the 2017 A/H7N9 IIV recognizes antigenically drifted variants of 
influenza A/H7 viruses in at least a subset of samples. Since antibodies targeting the NA may 
represent an independent correlate of protection against influenza infection [15, 16], the effect of 
adjuvant inclusion in the boost regimen on the magnitude and breadth of NA responses, as well 
as the effect of the inclusion of an adjuvant in the prime regimen on these responses will be 
evaluated. 
Based on previously conducted studies with a 2013 A/H7N9 IIV manufactured by Sanofi Pasteur 
administered with or without AS03, it is anticipated that one boosting dose of 2017 A/H7N9 IIV 
administered IM at the 3.75 mcg of HA dosage with or without AS03 adjuvant will be well-
tolerated and more immunogenic compared to one or two doses of the non-adjuvanted study 
vaccine in healthy adults. 


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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 
intramuscular (IM) injection, possible reactions to the 2017 H7N9 IIV, with 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 have an 
unknown health problem at the time of screening. This trial will screen by physical exam, 
history, vital signs and erythrocyte sedimentation rate (ESR). Clinical 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. 
There is potential for AEs to occur more frequently in the adjuvanted vaccine treatment arms 
[64] than in the non-adjuvanted treatment arms. 
The 2017 A/H7N9 IIV to be used in this clinical trial has not been tested for safety in animals; 
however, it is currently being evaluated in humans. The Division of Microbiology and Infectious 
Diseases (DMID), NIAID is sponsoring two Phase II clinical trials in healthy subjects to assess 
the safety, reactogenicity and immunogenicity of IM doses of the 2017 A/H7N9 IIV produced by 
Sanofi Pasteur, Swiftwater, PA, administered with or without the AS03 adjuvant produced by 
GSK and co-administered sequentially or simultaneously with licensed, seasonal influenza 
vaccine (Fluzone® Quadrivalent Influenza Vaccine) produced by Sanofi Pasteur, Swiftwater, PA 
(DMID Protocols: 17-0075; NCT03312231, 17-0077; NCT03318315). In addition, NIAID is 
sponsoring a third Phase II clinical trial in healthy subjects to assess the safety, reactogenicity 
and immunogenicity of two doses of the 2013 and 2017 A/H7N9 IIVs administered IM at 
different dosages with or without AS03 adjuvant using different prime-boost vaccination 
schedules (DMID Protocol 17-0078; NCT03589807). 
The 2017 A/H7N9 IIV is manufactured using the same procedures used to manufacture the 2013 


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A/H7N9 IIV. DMID, NIAID has sponsored at least five Phase II clinical trials to assess the 
safety, reactogenicity and immunogenicity of IM doses of the 2013 A/H7N9 IIV produced by 
Sanofi Pasteur, Swiftwater, PA, administered with or without either AS03 (GSK) or MF59 
(Seqirus) adjuvants in healthy subjects (DMID Protocols: 13-0032; NCT01938742, 13-0033; 
NCT01942265, 13-0034; NCT02213354, 13-0044; NCT02586792, and 14-0015; NCT02921997). 
Overall, the study products administered in 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 cases of autoimmune thyroiditis (Hashimoto’s disease/Hashimoto’s 
thyroiditis), classified as Adverse Events of Special Interest (AESIs), were reported in this 
clinical trial: one case was assessed as not related to study product (due to preexisting thyroid 
peroxidase antibodies) whereas the other case was assessed as related to study product (no 
preexisting thyroid peroxidase antibodies). 
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 
study vaccination, but both disorders received the diagnosis after study vaccination. 
For DMID Protocol 13-0034, seventy-five SAEs were reported. All were assessed as being not 
related to study product. Two AESIs were reported in this clinical trial: guttate psoriasis vulgaris 
and lichen planus; both were assessed as related to study product. 
For DMID Protocol 13-0044, no SAEs were reported. No AESIs were reported, since this 
clinical trial tested the unadjuvanted 2013 A/H7N9 IIV. 
For DMID Protocol 14-0015, one SAE was reported. It was assessed as not related to study 
product. No AESIs were reported in this clinical trial. 
The monovalent split 2017 A/H7N9 IIV to be used in this clinical trial was derived from the 
influenza virus A/Hong Kong/125/2017 (H7N9). The manufacturing process for the production 
of the 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. 
 
 
 


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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 their monovalent split 
2013 A/H7N9 IIV administered with or without AS03 or 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 
(itching), ecchymosis (bruising), erythema (redness), induration (hardness), edema (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 (GBS). 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. 


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During the swine influenza (A/H1N1) vaccine campaign of 1976, some recipients developed a 
paralytic illness called 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 
(A/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 [65]. Interestingly, although 
vaccination rates have increased in the last 10 years, the numbers of reported cases of vaccine-
associated GBS have declined [66]. A recent study in Canada showed that the 2009 A/H1N1 
vaccine was associated with a small but significant risk of GBS in persons 50 years of age and 
older [67]. An active, population-based surveillance study conducted in the US during the 2009-
2010 influenza season found less than 1 excess GBS case per million doses of 2009 A/H1N1 
vaccine administered – a rate similar to that associated with some previously administered 
annual influenza vaccines [68-70]. Another study using the Medicare system showed an elevated 
risk of GBS with monovalent 2009 A/H1N1 vaccination (incidence rate ratio = 2.41, 95% 
confidence interval (CI): 1.14, 5.11; attributable risk = 2.84 per million doses administered, 95% 
CI: 0.21, 5.48) [71]. An international collaboration study also supported a conclusion of an 
association between 2009 A/H1N1 vaccination and GBS [72]. It is unknown if the administration 
of the 2017 A/H7N9 IIV 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 GSK AS03 Adjuvant Investigator’s Brochure 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 injection site 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 AS03-
adjuvanted H5N1 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 


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surveillance data seen with unadjuvanted, IIV3s and (in the case of the A/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 increase, pain in extremity, 
polymyalgia rheumatica, and thrombocytopenia. Three occurred in recipients of unadjuvanted 
H1N1 vaccine: alanine aminotransferase increase, 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 [73]. 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 


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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 country 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). 
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 


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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) 
From post-marketing surveillance with inter-pandemic (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. 


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However, there are no available data related to the risks of exposure to the 2017 A/H7N9 IIV 
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 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. 
2.3.2 Known Potential Benefits 
There are no known benefits attributable to the receipt of the 2017 A/H7N9 IIV with or without 
AS03 adjuvant. Vaccination using the 2017 A/H7N9 IIV with or without AS03 adjuvant may or 
may not provide protection against a serious disease with the influenza 2017 A/H7N9 virus, 
should the subject be exposed. The duration of any such protection is currently unknown. The 
2017 A/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 strategy and the vaccine and adjuvant being evaluated in this clinical trial 
prove to be sufficiently safe and immunogenic and can be employed if a need for widespread 
influenza 2017 A/H7N9 vaccination occurs. 
 


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3 
STUDY OBJECTIVES AND OUTCOME MEASURES 
3.1 
Study Objectives 
3.1.1 Primary Objectives 
Safety: 
• To assess the safety and reactogenicity of 2017 A/H7N9 IIV given with or without AS03 
adjuvant following receipt of one dose of study vaccine. 
Immunogenicity: 
• To assess the serum hemagglutination inhibition (HAI) and neutralizing (Neut) antibody 
responses following receipt of the study vaccine. 
3.1.2 Secondary Objectives 
Safety: 
• To assess unsolicited non-serious adverse events (AEs) following receipt of the study 
vaccine. 
• To assess medically-attended adverse events (MAAEs), including new-onset chronic 
medical conditions (NOCMCs) and potentially immune-mediated medical conditions 
(PIMMCs), following receipt of the study vaccine. 
Immunogenicity: 
• To assess the kinetics and durability of serum HAI and Neut antibody responses 
following receipt of the study vaccine. 
3.1.3 Exploratory Objectives 
Immunogenicity: 
• To assess the effects of age, sex, body mass index (BMI), and prior receipt of seasonal or 
non-study pandemic influenza vaccine(s) on serum HAI and Neut antibody responses 
following receipt of the study vaccine. 


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• To determine, in at least a subset of samples, the serum antibody responses to N9 NA. 
• To assess, in at least a subset of samples, HA stem-specific antibody responses. 
• 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. 
3.2 
Study Outcome Measures 
3.2.1 Primary Outcome Measures 
Safety: 
• Occurrence of all serious adverse events (SAEs) from the time of study vaccination 
through approximately 12 months after study vaccination. 
• Occurrence of solicited injection site and systemic reactogenicity events from the time of 
study vaccination through 7 days after study vaccination. 
• Occurrence of clinical safety laboratory AEs from the time of study vaccination through 
approximately 7 days after study vaccination. 
Immunogenicity: 
• For HAI and Neut antibodies, percentage of subjects achieving seroconversion against 
the 2017 influenza A/H7N9 study vaccine virus (defined as either a pre-vaccination titer 
<10 and a post-vaccination titer ≥1:40 or a pre-vaccination titer ≥10 and a minimum four-
fold rise in post-vaccination antibody titer) approximately 21 days after study 
vaccination. 
• For HAI and Neut antibodies, percentage of subjects achieving titer ≥40 against the 2017 
influenza A/H7N9 study vaccine virus approximately 21 days after study vaccination. 
• Geometric mean titers (GMTs) of serum HAI and Neut antibodies against the 2017 
influenza A/H7N9 study vaccine virus approximately 21 days after study vaccination. 
 
 


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3.2.2 Secondary Outcome Measures 
Safety: 
• Occurrence of all unsolicited non-serious AEs from the time of study vaccination through 
approximately 21 days after study vaccination. 
• Occurrence of all MAAEs, including NOCMCs and PIMMCs, from the time of study 
vaccination through approximately 12 months after study vaccination. 
Immunogenicity: 
• For HAI and Neut antibodies, percentage of subjects seroconverting against the 2017 
influenza A/H7N9 study vaccine virus approximately 7 and 180 days after study 
vaccination. 
• For HAI and Neut antibodies, percentage of subjects achieving a titer ≥40 against the 
2017 influenza A/H7N9 study vaccine virus approximately 7 and 180 days after study 
vaccination. 
• GMTs of serum HAI and Neut antibodies against the 2017 influenza A/H7N9 study 
vaccine virus approximately 7 and 180 days after study vaccination. 
• The percentage of subjects seroconverting, the percentage of subjects achieving a titer 
≥40, and the GMTs of serum HAI and Neut antibodies against the 2013 influenza 
A/H7N9 vaccine virus (priming vaccine virus) approximately 21 days after study 
vaccination. 
3.2.3 Exploratory Outcome Measures 
Immunogenicity: 
• For HAI and Neut antibodies, GMTs and percentage of subjects seroconverting against 
the 2017 influenza A/H7N9 study vaccine virus approximately 21 days after study 
vaccination, by age, sex, BMI, the inclusion of an adjuvant in the prime and/or boost 
regimens, and prior receipt of seasonal or non-study pandemic influenza vaccine(s). 
• GMTs and percentage of subjects seroconverting (defined as four-fold change from 
baseline) of serum anti-NA (by enzyme-linked immunosorbent assay [ELISA]) or anti-
neuraminidase inhibition (NAI) (by enzyme-linked lectin assay [ELLA]) antibodies 
immediately prior to and 7, 21 and 180 days after study vaccination. 


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• Correlation between the inclusion of an adjuvant in the prime and/or boost regimens with 
the elicited H7 HA and N9 NA-specific serum antibody titers approximately 21 days 
after study vaccination. 
• GMTs of HA stem-specific antibody immediately prior to and approximately 7, 21 and 
180 days after study vaccination. 
• For HAI and Neut antibodies, GMTs and percentage of subjects seroconverting against 
antigenically drifted variants of influenza A/H7 viruses approximately 21 days after study 
vaccination. 
 


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4 
STUDY DESIGN 
This is a Phase II clinical trial in up to 420 males and non-pregnant females, 19 to 70 years of 
age, inclusive, who are in good health and meet all eligibility criteria, which include a screening 
erythrocyte sedimentation rate (ESR) laboratory evaluation. This clinical trial is designed to 
assess the safety, reactogenicity and immunogenicity of one dose of a monovalent inactivated 
split influenza 2017 A/H7N9 virus vaccine (2017 A/H7N9 IIV) manufactured by Sanofi Pasteur 
(SP), administered intramuscularly (IM) at 3.75 mcg hemagglutinin (HA) per dose, given with or 
without AS03 adjuvant manufactured by GlaxoSmithKline Biologicals (GSK), to subjects 
primed with a monovalent inactivated split influenza 2013 A/H7N9 virus vaccine (2013 A/H7N9 
IIV) in DMID Protocols 13-0032 and 13-0033, or to those who are A/H7 IIV-naïve. Phosphate 
buffered saline (PBS) diluent manufactured by Patheon Manufacturing Services LLC will be 
used to achieve the targeted dosage. 
Subjects who received the 2013 A/H7N9 IIV in DMID Protocols 13-0032 and 13-0033 or are 
A/H7 IIV-naïve will be stratified by prior receipt of 2013 A/H7N9 IIV, as well as by site and 
prior receipt of licensed, seasonal influenza vaccine (defined as receipt of at least one of the 
2017-2018 and/or 2018-2019 licensed, seasonal influenza vaccines versus none), then randomly 
assigned in a 1:1 ratio to 1 of 2 treatment arms to receive 1 dose of 2017 A/H7N9 IIV at 3.75 
mcg HA per dose with or without AS03 adjuvant (see Table 1). 
Reactogenicity will be measured by the occurrence of solicited injection site and systemic 
reactions from the time of study vaccination through 7 days after study vaccination. Unsolicited 
non-serious adverse events (AEs) will be collected from the time of study vaccination through 
approximately 21 days after study vaccination. Serious adverse events (SAEs) and medically-
attended adverse events (MAAEs), including new-onset chronic medical conditions (NOCMCs) 
and potentially immune-mediated medical conditions (PIMMCs), will be collected from the time 
of study vaccination through approximately 12 months after study vaccination. Clinical safety 
laboratory evaluations (hematology and chemistry) will be performed on venous blood collected 
immediately prior to study vaccination and approximately 7 days after study vaccination. 
Immunogenicity testing will include performing serological assays to assess hemagglutination 
inhibition (HAI), neutralizing (Neut), neuraminidase inhibition (NAI), neuraminidase (NA)-
specific, and HA stem-specific antibody titers at multiple time points following each study 
vaccination. Venous blood will also be collected at multiple time points following study 
vaccination for the future research use of serum, plasma and peripheral blood mononuclear cells 
(PBMCs). 
Correlation of the H7 HA and N9 NA-specific serum antibody responses to the inclusion of an 
adjuvant in the prime and/or boost regimens will also be determined. 


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For additional details on study procedures and evaluations and study schedule by study 
visits/days, see Sections 7 and 8 as well as Appendix A: Schedule of Study Procedures and 
Evaluations. 
 


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5 
STUDY ENROLLMENT AND WITHDRAWAL 
Up to 420 males and non-pregnant females, 19 to 70 years of age, inclusive, who are in good 
health and meet all eligibility criteria will be enrolled at up to 9 VTEU sites (including their 
subcontractors) participating in this trial. The target population includes recipients of 2013 
A/H7N9 IIV with or without AS03 or MF59 in DMID Protocols 13-0032 and 13-0033 or 
influenza A/H7-naïve, and should reflect the community at large at each of the participating 
VTEU sites. Estimated time to complete enrollment in this trial is approximately 16 weeks. 
Subjects in DMID Protocols 13-0032 and 13-0033 who were recipients of the 2013 A/H7N9 IIV 
and agreed to future contact will be given information regarding this trial, as well as potential 
subjects who have previously participated in vaccine trials conducted at each of the participating 
VTEU sites. Other forms and/or mechanisms of recruitment may also be used. The 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 (PI) 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. Must agree to the collection of venous blood per protocol. 
4. Must agree to have residual specimens and samples/specimens collected during this trial 
specifically for the purpose of future research stored for future research use. 
5. Are males or non-pregnant females, 19 to 70 years of age, inclusive. 
6. Are in good health1. 


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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, emergency room 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 inclusion criterion. Any change in prescription medication due to improvement of a 
disease outcome, as determined by the site PI 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 PI 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 
(except inhaled corticosteroids as outlined in the Subject Exclusion Criteria (see Section 5.1.2)) as well as herbals, 
vitamins and supplements are permitted. 
7. Oral temperature is less than 100.0°F. 
8. Pulse is 47 to 100 beats per minute, inclusive. 
9. Systolic blood pressure is 85 to 150 mmHg, inclusive. 
10. Diastolic blood pressure is 55 to 95 mmHg, inclusive. 
11. ESR is less than 30 mm per hour. 
12. Women of childbearing potential2 must use an acceptable contraception method3 from 30 
days before study vaccination until 60 days after 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 has passed since 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 study vaccination, barrier methods such as condoms or diaphragms/cervical cap with spermicide, effective 
intrauterine devices, NuvaRing®, and licensed hormonal methods such as implants, injectables or oral contraceptives 
(“the pill”). 
13. Women of childbearing potential must have a negative urine or serum pregnancy test 
within 24 hours prior to study vaccination. 
14. Received 1 or 2 doses of 2013 A/H7N9 IIV with or without AS03 or MF59 adjuvant in 
DMID Protocols 13-0032 or 13-0033, or are A/H7 IIV-naïve. 


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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 PI 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 PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety 
parameters as required by the protocol. 
2. Have any medical disease or condition that, in the opinion of the site PI 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 cytotoxic anticancer chemotherapy or radiation therapy 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 GBS. 
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 (PIMMCs). 


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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 interfere7 with subject compliance or safety evaluations. 
7As determined by the site PI or appropriate sub-investigator. 
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. 
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 corticosteroids8 within 30 days prior to study vaccination. 
8High-dose defined as per age as using inhaled high-dose per reference chart in the National Heart, Lung and Blood 
Institute Guidelines for the Diagnosis and Management of Asthma (EPR-3) or other lists published in UPTODATE. 
18. Received or plan to receive a licensed, live vaccine within 30 days before or after study 
vaccination. 
19. Received or plan to receive a licensed, inactivated vaccine (excluding all licensed, 
seasonal IIVs) within 14 days before or after study vaccination. 
20. Received or plan to receive a licensed, seasonal IIV within 21 days before or after study 
vaccination. 
21. Received immunoglobulin or other blood products (except Rho D immunoglobulin) 
within 90 days prior to study vaccination. 
22. Received an experimental agent9 within 30 days prior to study vaccination or expect to 
receive an experimental agent10 during the trial-reporting period11. 
9Including vaccine, drug, biologic, device, blood product, or medication. 
10Other than from participation in this trial. 
11Approximately 12 months after study vaccination. 
23. Are participating or plan to participate in another clinical trial with an interventional 
agent12 that will be received during the trial-reporting period13. 
12Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication. 
13Approximately 12 months after study vaccination. 


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24. Have a history of influenza A/H7 subtype infection. 
25. Had substantial direct contact14 with live or freshly slaughtered poultry or pigeons while 
in mainland China within the past five years. 
14Substantial direct contact is defined as visited a poultry farm and/or a live poultry market. 
26. Occupational exposure to or substantial direct physical contact15 with birds in the past 
year and through 21 days after study vaccination. 
15Exposure 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. 
28. Plan to travel outside the US (continental US, Hawaii and Alaska) from the time of study 
vaccination through 21 days after study vaccination. 
5.2 
Treatment Assignment Procedures 
5.2.1 Enrollment and Randomization Procedures 
Per ICH E6 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 and randomly assigned in a 1:1 ratio to 1 of 2 treatment arms, 
stratified by prior receipt of 2013 A/H7N9 IIV , as well as by site and prior receipt of licensed, 
seasonal influenza vaccine (defined as receipt of at least one of the 2017-2018 and/or 2018-2019 
licensed, seasonal influenza vaccines versus none). 
Subjects will receive one of two study products per their randomized treatment: 2017 A/H7N9 
IIV at 3.75 mcg HA per dose with or without AS03 adjuvant (see Table 1). 
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. 


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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. 
5.2.2 Masking Procedures 
This is a double-blinded clinical trial. 
Subjects, site investigators and study personnel performing any study-related assessments 
following study vaccine administration to the subject are blinded to treatment assignment. 
Laboratory personnel performing HAI and Neut antibody assays will receive serum specimens 
blinded to subject ID number and specimen visit number. 
The randomization scheme will be generated by the SDCC and provided to unblinded study 
personnel (i.e., research pharmacists performing study product preparations and unblinded study 
vaccine administrators) at the participating VTEU sites. 
The unblinded study product 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 to the subject. 
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 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. 
5.2.3 Reasons for Withdrawals and Discontinuation of Study Product Administration 
Subjects may voluntarily withdraw their consent for trial participation at any time and for any 
reason, without penalty or loss of benefits to which they are otherwise entitled. 
The site PI or appropriate sub-investigator may also withdraw a subject from receiving the study 
vaccine for any reason. 
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 PI or appropriate sub-investigator, would 


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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). 
• Subject withdrawal of consent. 
• Subject lost to follow-up. 
• Termination of this trial. 
• As deemed necessary by the site PI or appropriate sub-investigator for noncompliance or 
other reasons. 
• New information becomes available that makes further participation unsafe. 
5.2.4 Handling of Withdrawals and Discontinuation of Study Product Administration 
The primary reason for withdrawal from this trial will be recorded on the Study Status data 
collection form (DCF). Subjects will be encouraged to complete the Early Termination Visit. 
The Early Termination Visit procedures are listed in Section 8.4. 
Subjects are free to withdraw at any time or may be withdrawn by the site PI or appropriate sub-
investigator at any time (see Section 5.2.3). Subjects who withdraw after screening but before 
receiving the study vaccine will receive no further follow up. Subjects who withdraw after 
receiving 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 study vaccination. These subjects will also be encouraged to 
provide a venous blood sample for serological assays approximately 21 and 180 days after their 
study vaccination, if feasible. 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, and 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 


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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. 
The site PI or appropriate sub-investigator will inform the subject that already collected data will 
be retained and analyzed even if the subject withdraws or is withdrawn from this study. 
5.2.5 Subject Replacement 
Subjects who withdraw, or are withdrawn or terminated from this trial, or are lost to follow-up 
after signing the informed consent form (ICF), randomization and receipt of study vaccine will 
not be replaced. However, if a subject withdraws after signing the ICF, but before randomization 
and/or receipt of study vaccine, they may be replaced. 
5.2.6 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. 
If this trial is prematurely terminated by the sponsor, any regulatory authority, the site PI, or 
appropriate sub-investigator for any reason, the site PI or appropriate sub-investigator will 
promptly inform the subjects and assure appropriate therapy or follow-up for the subjects, as 
necessary. The site PI or appropriate sub-investigator will provide a detailed written explanation 
of the termination to the IRB. 
 


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6 
STUDY INTERVENTION/INVESTIGATIONAL 
PRODUCT 
6.1 
Study Product Description 
2017 A/H7N9 IIV 
Sanofi Pasteur has developed a monovalent split 2017 A/H7N9 IIV manufactured using a reverse 
genetics-derived reassortant candidate vaccine virus, IDCDC RG56B (H7N9), containing the HA 
and NA from low pathogenic avian 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 processes used 
for the investigational vaccine are similar to the Fluzone® family of licensed processes. 
 
 
 
 
 
PBS Diluent 
The PBS diluent was manufactured by Patheon Manufacturing Services LLC in accordance with 
Good Manufacturing Practice Regulations. 
AS03 Adjuvant [Adjuvant System (03)] 
6.1.1 Acquisition 
2017 A/H7N9 IIV will be provided by Sanofi Pasteur under contract to BARDA/DHHS. 
AS03 adjuvant will be provided by GSK under contract to BARDA/DHHS. 
Upon request by DMID, 2017 A/H7N9 IIV and AS03 adjuvant will be transferred to the 
following address: 


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DMID Clinical Materials Services Contract 
Fisher BioServices 
20439 Seneca Meadows Parkway 
Germantown, MD 20876 
Phone: 240-477-1350 
Fax: 240-477-1360 
Email: DMID.CMS@thermofisher.com 
PBS diluent and sterile empty vials (2-mL, 3-mL or 5-mL) for admixing will be obtained by the 
DMID Clinical Materials Services (CMS) Contract, Fisher BioServices. 
2017 A/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 PI require 
additional 2017 A/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 A/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. Antibiotics are not used in the manufacture of 
this vaccine. This vaccine contains no preservative (thimerosal). There is no gelatin added to this 
vaccine in the manufacturing process. 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. 
 
 
 
 
 
 
Detailed mixing instructions to achieve the targeted dosage are included in the protocol-specific 
MOP. 


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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 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 manufacturers’ Investigator’s Brochures 
for the A/H7N9 IIV and AS03 adjuvant as well as in the protocol-specific MOP. 
Sterile empty vials (2-mL, 3-mL or 5-mL) 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 course 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 participating VTEU site’s research pharmacist must alert 
the site PI 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 PI 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, 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. Additional instructions for quarantine and DMID contact 
information are provided in the protocol-specific MOP. 


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6.2 
Dosage, Preparation and Administration of Study 
Intervention/Investigational Product 
Dosage calculations are based on the actual HA content per 0.5 mL. Each 0.5 mL dose of AS03-
adjuvanted study vaccine contains one dose (0.25 mL) of AS03 adjuvant. 
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’s research pharmacist on the same day of study 
vaccine administration to the subject. 
Visually inspect the 2017 A/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(s) visible particulate matter, or if there are any concerns regarding the 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 PI 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 the affected study product(s) cannot be used, the site will receive specific 
instructions on how to return the affected study product(s) to the DMID CMS or destroy the 
affected study product(s) on site. If the 2017 A/H7N9 IIV, PBS diluent or 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 PBS diluent, visually inspect the A/H7N9 IIV plus 
PBS diluent admixture (intermediate or final mixed vial depending on treatment arm) prior to 
use. The A/H7N9 IIV plus PBS diluent admixture will be essentially clear and slightly 
opalescent in color. For those doses that must be admixed with PBS diluent and AS03 adjuvant, 
visually inspect the A/H7N9 IIV/PBS diluent plus AS03 adjuvant admixture (final mixed vial) 
prior to use. The A/H7N9 IIV/PBS diluent plus AS03 adjuvant admixture will be milky (whitish 
to yellowish) in color. If the admixture(s) appear(s) to have been damaged, contaminated or 
discolored, contain(s) visible particulate matter, or if there are any concerns regarding the 
integrity, do NOT use the affected admixture(s). The affected admixture(s) must be quarantined 
at 2°C to 8°C (36°F to 46°F) for the A/H7N9 IIV plus PBS diluent admixture or room 
temperature for the A/H7N9 IIV/PBS diluent plus AS03 adjuvant and labeled as ‘Do Not Use’ 
(until further notice). The site PI or responsible person should immediately contact the DMID 
Product Support Team at DMIDProductSupportTeam@niaid.nih.gov and DMID Clinical Project 


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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 admixture(s) can be used. If the affected admixture(s) cannot be used, the site will 
receive specific instructions on how to send the affected admixture(s) to the DMID CMS or 
destroy the affected admixture(s) on site. If the affected admixture is unusable, the participating 
VTEU site’s research pharmacist will prepare another admixture. Additional instructions for 
quarantine and DMID contact information are provided in the protocol-specific MOP. 
For those doses that must be admixed with PBS diluent, the A/H7N9 IIV plus PBS diluent 
admixture (intermediate or final mixed vial depending on treatment arm), once mixed, must be 
stored at 2°C to 8°C (36°F to 46°F) in an upright position and must be used within 8 hours. For 
those doses that must be admixed with PBS diluent and AS03 adjuvant, the A/H7N9 IIV/PBS 
diluent plus AS03 adjuvant admixture (final mixed vial), once mixed, must be stored at room 
temperature in an upright position and must be used within 8 hours. 
Only one- 0.5 mL dose of study vaccine should be withdrawn from the intermediate and final 
mixed vial(s). Gently invert the intermediate and final mixed vial(s) 5 to 7 times immediately 
before the single 0.5 mL dose of study vaccine is withdrawn. Do not shake the intermediate 
and final mixed vial(s). 
Study vaccine administration to the subject 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 to the subject. One- 0.5 mL dose of study vaccine will be 
administered to the subject via a single IM injection into the deltoid muscle of the subject’s 
preferred arm. See the protocol-specific MOP for information on how to administer IM 
injections. The site of injection (right or left arm) and time of study vaccine administration to the 
subject will be recorded on the appropriate DCF. 
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 1-mL 
disposable, sterile syringe. 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. 
6.3 
Modification of Study Intervention/Investigational Product for a 
Subject 
Each enrolled subject will receive one study vaccination and there will be no dose modifications. 


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6.4 
Accountability Procedures for the Study Intervention/Investigational 
Product 
After receipt of the 2017 A/H7N9 IIV, PBS diluent, AS03 adjuvant, and sterile empty vials, the 
site PI is responsible for study product distribution and disposition, and has ultimate 
responsibility for study product accountability. The site PI may delegate to the participating 
VTEU site’s research pharmacist responsibility for study product accountability. The 
participating VTEU site’s 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). Study product accountability records 
and dispensing logs will also capture vial numbers, including intermediate and final mixed vial 
numbers, 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 recorded on the appropriate DCF. All study product(s), including the amount of 
2017 A/H7N9 IIV, PBS diluent, AS03 adjuvant, and admixtures, 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 site’s study product 
accountability records and dispensing logs per the site monitoring plan. 
Used and unused vials of 2017 A/H7N9 IIV, PBS diluent, AS03 adjuvant, and admixtures will 
be retained until monitored and released for disposition, as applicable. This can occur on an 
ongoing basis for used vials of 2017 A/H7N9 IIV, PBS diluent, AS03 adjuvant, and admixtures. 
Used vials of 2017 A/H7N9 IIV, PBS diluent, AS03 adjuvant, and admixtures 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 A/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 vaccine will be administered to the subject by an unblinded study vaccine administrator 
via IM injection per the subject’s randomized treatment assignment and as described in Section 
6.2. Thus, subject compliance is not anticipated to be an issue. Study vaccine administration to 
the subject will be recorded on the appropriate DCF. 


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6.6 
Concomitant Medications/Treatments 
Administration of medications, therapies or vaccines will be recorded on the appropriate DCF. 
Concomitant medications will include all current medications and medications taken in the 60 
days prior to signing the ICF through approximately 21 days after study vaccination or early 
termination (if prior to 21 days after study vaccination), whichever occurs first. Medications 
reported in the electronic case report form (eCRF) are limited to those taken within 30 days prior 
to study vaccination through approximately 21 days after study vaccination. Prescription and 
over-the-counter drugs will be included as well as herbals, vitamins and supplements. In 
addition, receipt of any non-study influenza vaccines will be solicited through approximately 180 
days after 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 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 PI 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/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 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 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 clinic visits after study vaccination, an interim 
medical history will be obtained by interview of subjects and any changes since the previous 
clinic visit or phone call will be noted. 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 on Day 1 prior to study vaccination, a physical examination 
will be performed on all subjects, by a study clinician licensed to make medical diagnoses and 
listed on the Form FDA 1572 as the site PI or sub-investigator, 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 PIMMCs. At follow-up clinic visits 
after 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 PI or sub-investigator. Targeted physical 
examinations should also include an assessment for signs suggestive of PIMMCs. 
Vital signs (oral temperature, pulse and blood pressure [BP]) will be collected at the screening 
visit (optional) and prior to study vaccination. Vital signs may be obtained if indicated at 
approximately 1, 3 and 7 days after study vaccination (this may only occur approximately 7 days 
after study vaccination for sites not processing blood for PBMCs isolation). Vital signs assessed 
on Day 1 prior to 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 study 
vaccination for the calculation of BMI. 
Reactogenicity assessments will include an assessment of solicited AEs occurring from the time 
of study vaccination through 7 days after study vaccination, which includes an assessment of 


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injection site reactions including pruritus, ecchymosis, erythema, induration, edema, pain, and 
tenderness as well as systemic reactions including fever, feverishness, fatigue, malaise, myalgia, 
arthralgia, headache, and nausea. Pre-administration reactogenicity assessments will be 
performed immediately prior to 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 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 DCF prior to discharge from 
the clinic. The study vaccination site will also be examined approximately 1, 3 and 7 days after 
study vaccination (this will only occur approximately 7 days after study vaccination for sites not 
processing blood for PBMCs isolation). 
All subjects will complete a Memory Aid from the time of study vaccination through 7 days after 
study vaccination. Memory Aids will be reviewed with the subjects for any AEs (solicited 
injection site and systemic reactions as well as unsolicited AEs), SAEs and concomitant 
medications (including solicitation for receipt of any non-study influenza vaccines) 
approximately 1, 3 and 7 days after study vaccination via phone call or clinic visit. 
7.2 
Laboratory Evaluations 
Clinical laboratory evaluations and special assays are described below. Refer also to Sections 4 
and 8 as well as Appendix A: Schedule of Study Procedures and Evaluations. 
7.2.1 Clinical Laboratory Evaluations 
Urine or serum pregnancy tests will be performed locally by the site at the screening visit 
(optional) and within 24 hours prior to study vaccination for all women of childbearing potential. 
Results must be negative and known prior to randomization on Day 1 and administration of 
study vaccination to be eligible for participation in this trial and receipt of study vaccine. 
The ESR evaluation will be performed locally by the site at the screening visit (optional) or on 
Day 1 prior to study vaccination. Results must be known prior to randomization on Day 1 and 
administration of study vaccination, and confirmed as less than 30 mm per hour to be eligible for 
participation in this trial and receipt of study vaccine. 
Clinical safety laboratory parameters (WBC, Hgb, PLT, ALT, T. Bili, Cr) will be collected prior 
to study vaccination and approximately 7 days after study vaccination. These evaluations will be 
performed by the central (clinical) laboratory. The results from the clinical safety laboratory 


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parameters collected on Day 1 prior to study vaccination will not be available or reviewed prior 
to study vaccination, and will serve as a baseline safety assessment only. 
The volume of venous blood to be collected for ESR and clinical safety laboratory evaluations is 
presented in Table 3. 
7.2.2 Special Assays or Procedures 
Serological Assays 
Once the last subject completes the visits that occur through approximately 21 days after study 
vaccination, serum specimens collected for these visits will be shipped from the DMID CMS to 
specified research laboratories for serological analysis. Once the last subject completes the visit 
that occurs approximately 180 days after study vaccination, serum specimens collected for this 
visit will be shipped from the DMID CMS to specified research laboratories to conduct the final 
serological analyses. 
HAI and Neut Antibody Assays 
Assays to determine serum levels of HAI and Neut antibodies will be performed by Southern 
Research on specimens collected at multiple time points prior to and following study 
vaccination. Subjects who withdraw early will have these assays run on available sera. 
HA Stem-Specific Assays 
Assays to determine and quantitate HA stem-specific antibodies are in development, and the 
specified research laboratories for this assessment are to be determined. It is anticipated that 
serum levels of anti-HA stem-specific antibodies will be determined from specimens collected at 
multiple time points prior to and following study vaccination. Subjects who withdraw early will 
have these assays run on available sera. 
NA-Specific Assays 
Assays to determine the N9 NA-specific serum antibody responses are in development, and the 
specified research laboratory for this assessment is to be determined. 
Correlation of the H7 HA and N9 NA-specific serum antibody responses to the inclusion of an 
adjuvant in the prime and/or boost regimens will also be determined from specimens collected at 
multiple time points prior to and following study vaccination. 


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Any research laboratory involved with the determination of HA stem-specific and N9 NA-
specific serum antibody responses will remain blinded to the results from the HAI and Neut 
antibody assays performed by Southern Research. 
Venous blood will also be collected at multiple time points following study vaccination for the 
future research use of serum, plasma and PBMCs, and shipped to the DMID CMS for storage. 
The volume of venous blood to be collected for serological assays and future research is 
presented in Table 3. 
 
 




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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. 
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 clinical 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 additional serological assays will be shipped from the participating VTEU sites to 
the DMID CMS, and then provided by the DMID CMS to the specified research laboratories in a 
blinded manner. 
Specimens (sera, plasma and PBMCs) for future research will be shipped from the participating 
VTEU sites to the DMID CMS. 
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 as well as Appendix A: Schedule of Study Procedures and Evaluations. 
8.1 
Screening (Optional) and Enrollment Visits 
8.1.1 Visit 00, Screening (Day -28 to -1), Clinic Visit, Optional 
• Subjects will be provided with a description of this trial (purpose and study procedures) 
and asked to read and sign the ICF. The ICF will be signed prior to performing any study 
procedures, including administration of study vaccination. 
• Demographic information will be obtained by interview of subjects. 
• Eligibility criteria will be reviewed with subjects to ensure eligibility. 
• Complete medical history will be obtained by interview of subjects to ensure eligibility. 
• All concomitant medications taken within 60 days prior to signing the ICF 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 study 
vaccination. 
• Subject receipt of licensed, seasonal influenza vaccine over the current (2018-2019) and 
previous influenza season (2017-2018), what type (inactivated or live attenuated) and 
approximate date of vaccination will be recorded on the appropriate DCF, 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 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. Prior 
receipt of non-seasonal influenza vaccine is not exclusionary (see Section 5.1.2). 
• Vital signs, including oral temperature, pulse and BP, will be obtained to ensure 
eligibility. 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 for the calculation of BMI. 


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• 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 PIMMCs, by a 
study clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as 
the site PI or sub-investigator. 
• A urine or serum pregnancy test may be performed locally by the site for 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 to ensure 
eligibility. 
8.1.2 Visit 01, Day 1, Enrollment (for subjects previously screened at Day -28 to -1) and 
Study Vaccination, 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 study vaccination. 
• Eligibility criteria, including results of the ESR evaluation, will be reviewed with subjects 
prior to study vaccination to ensure continued eligibility. The ESR value must be 
confirmed as less than 30 mm per hour prior to randomization. 
• 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 study vaccination. Any changes in medical history since the screening 
visit will be reviewed with subjects prior to study vaccination to ensure continued 
eligibility. 
• All concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines) will be reviewed with subjects prior to study vaccination for accuracy and 
completeness. Any new concomitant medications taken since the screening visit will be 
reviewed with subjects prior to study vaccination to ensure continued eligibility. 
Medications reported in the eCRF are limited to those taken within 30 days prior to study 
vaccination. 
• Vital signs, including oral temperature, pulse and BP, will be obtained prior to study 
vaccination to ensure continued eligibility. Vital signs assessed on Day 1 prior to study 


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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. 
• A targeted physical examination, including an assessment for signs suggestive of 
PIMMCs, may be performed prior to 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 PI or sub-investigator. 
• A urine or serum pregnancy test will be performed locally by the site within 24 hours 
prior to study vaccination for all women of childbearing potential. Results must be 
negative and known prior to randomization and study vaccination. 
• Subjects will be enrolled in AdvantageEDCSM and randomly assigned to a treatment arm 
prior to study vaccination. 
• Approximately 10 mL of venous blood will be collected immediately prior to study 
vaccination for baseline clinical safety labs (WBC, Hgb, PLT, ALT, T. Bili, Cr) to be 
performed by the central (clinical) laboratory. The results from these evaluations will not 
be available or reviewed prior to study vaccination, and will serve as a baseline safety 
assessment only. 
• Approximately 15 mL of venous blood will be collected immediately prior to study 
vaccination for baseline serological assays. Approximately 5 mL of this venous blood 
sample will be designated for future research. 
• At sites processing blood for PBMCs isolation, approximately 80 mL of venous blood 
will be collected immediately prior to study vaccination for future research. 
• Pre-administration reactogenicity assessments will be performed immediately prior to 
study vaccination to establish baseline. 
• Subjects will then receive one- 0.5 mL dose of study vaccine via a single IM injection 
into the deltoid muscle of the subjects’ preferred arm. The site of injection (right or left 
arm) and time of study vaccine administration to the subject will be recorded on the 
appropriate DCF. Subjects will be observed in the clinic for at least 20 minutes after 
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 DCF prior to discharge from the clinic. 


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• Subjects will be provided with a Memory Aid and other study-related materials to record 
daily oral temperature, solicited injection site and systemic reactions, 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 study vaccination. If the site PI 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 Study Vaccination, Clinic Visit 
• Subjects will be provided with a description of this trial (purpose and study procedures) 
and asked to read and sign the ICF. The ICF will be signed prior to performing any study 
procedures, including administration of study vaccination. 
• Demographic information will be obtained by interview of subjects prior to study 
vaccination. 
• Eligibility criteria will be reviewed with subjects prior to study vaccination to ensure 
eligibility. 
• Complete medical history will be obtained by interview of subjects prior to study 
vaccination to ensure eligibility. 
• All concomitant medications taken within 60 days prior to signing the ICF will be 
reviewed with subjects prior to study vaccination to determine stability of chronic 
diseases and eligibility. Medications reported in the eCRF are limited to those taken 
within 30 days prior to study vaccination. 
• Subject receipt of licensed, seasonal influenza vaccine over the current (2018-2019) and 
previous influenza season (2017-2018), what type (inactivated or live attenuated) and 
approximate date of vaccination will be recorded on the appropriate DCF, 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 vaccine, including those that are experimental, 


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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 vaccine is not exclusionary (see Section 5.1.2). 
• Vital signs, including oral temperature, pulse and BP, will be obtained prior to study 
vaccination to ensure eligibility. Vital signs assessed on Day 1 prior to 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 prior to study vaccination for the calculation of BMI. 
• A physical examination will be performed on all subjects prior to study vaccination 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 PIMMCs, by a study clinician licensed to make medical diagnoses and 
listed on the Form FDA 1572 as the site PI or sub-investigator. 
• A urine or serum pregnancy test will be performed locally by the site within 24 hours 
prior to study vaccination for all women of childbearing potential. Results must be 
negative and known prior to randomization and study vaccination. 
• Approximately 4 mL of venous blood will be collected for ESR, and performed locally 
by the site prior to study vaccination. The ESR value must be confirmed as less than 30 
mm per hour prior to randomization and study vaccination. 
• Subjects will be enrolled in AdvantageEDCSM and randomly assigned to a treatment arm 
prior to study vaccination. 
• Approximately 10 mL of venous blood will be collected immediately prior to study 
vaccination for baseline clinical safety labs (WBC, Hgb, PLT, ALT, T. Bili, Cr) to be 
performed by the central (clinical) laboratory. The results from these evaluations will not 
be available or reviewed prior to study vaccination, and will serve as a baseline safety 
assessment only. 
• Approximately 15 mL of venous blood will be collected immediately prior to study 
vaccination for baseline serological assays. Approximately 5 mL of this venous blood 
sample will be designated for future research. 
• At sites processing blood for PBMCs isolation, approximately 80 mL of venous blood 
will be collected immediately prior to study vaccination for future research. 


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• Pre-administration reactogenicity assessments will be performed immediately prior to 
study vaccination to establish baseline. 
• Subjects will then receive one- 0.5 mL dose of study vaccine via a single IM injection 
into the deltoid muscle of the subjects’ preferred arm. The site of injection (right or left 
arm) and time of study vaccine administration to the subject will be recorded on the 
appropriate DCF. Subjects will be observed in the clinic for at least 20 minutes after 
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 DCF 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, 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 study vaccination. If the site PI 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 2, Clinic Visit 
(Window: Day 2+1 day post 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 phone call will be noted. 
• Concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines) will be recorded on the appropriate DCF. 
• All AE/SAEs will be recorded on the appropriate DCF. 


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• Memory Aid information will be reviewed with subjects. 
• Vital signs, including oral temperature, pulse and BP, 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 PI or sub-investigator. 
• The study vaccination site will be examined. 
• At sites processing blood for PBMCs isolation, approximately 16 mL of venous blood 
will be collected for future research. 
Note: This visit may be performed as a phone call assessment for sites not processing blood for 
PBMCs isolation. Study personnel will contact these subjects by phone to review their Memory 
Aid information and solicit any AE/SAEs and concomitant medications (including solicitation 
for receipt of any non-study influenza vaccines). Based on the information collected, subjects 
may be asked to return to the clinic for evaluation. 
8.2.2 Visit 03, Day 4, Clinic Visit 
(Window: Day 4+1 day post 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 phone call will be noted. 
• Concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines) will be recorded on the appropriate DCF. 
• All AE/SAEs will be recorded on the appropriate DCF. 
• Memory Aid information will be reviewed with subjects. 
• Vital signs, including oral temperature, pulse and BP, 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. 


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• 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 PI or sub-investigator. 
• The study vaccination site will be examined. 
• At sites processing blood for PBMCs isolation, approximately 24 mL of venous blood 
will be collected for future research. 
Note: This visit may be performed as a phone call assessment for sites not processing blood for 
PBMCs isolation. Study personnel will contact these subjects by phone to review their Memory 
Aid information and solicit any AE/SAEs and concomitant medications (including solicitation 
for receipt of any non-study influenza vaccines). Based on the information collected, subjects 
may be asked to return to the clinic for evaluation. 
8.2.3 Visit 04, Day 8, Clinic Visit 
(Window: Day 8-1/+2 days post 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 phone call will be noted. 
• All concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines) will be recorded on the appropriate DCF. 
• All AE/SAEs will be recorded on the appropriate DCF. 
• Memory Aid information will be reviewed with subjects. 
• Vital signs, including oral temperature, pulse and BP, 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 PI or sub-investigator. 
• The study vaccination site will be examined. 


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• Approximately 10 mL of venous blood will be collected for clinical safety labs (WBC, 
Hgb, PLT, ALT, T. Bili, Cr) to be performed by the central (clinical) laboratory. 
• Approximately 15 mL of venous blood will be collected for serologic assays. 
Approximately 5 mL of this venous blood sample will be designated for future research. 
• At sites processing blood for PBMCs isolation, approximately 64 mL of venous blood 
will be collected for future research. 
Note: Subjects that complete this visit on Day 7 will be reminded to complete their Memory Aid 
through the end of Day 8, and study personnel will contact these subjects by phone to review 
their Memory Aid information and solicit any AE/SAEs and concomitant medications (including 
solicitation for receipt of any non-study influenza vaccines). Based on the information collected, 
subjects may be asked to return to the clinic for evaluation. 
8.2.4 Visit 05, Day 15, Clinic Visit 
(Window: Day 15±1 day post 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 phone call will be noted. 
• All concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines) will be recorded on the appropriate DCF. 
• All AE/SAEs will be recorded on the appropriate DCF. 
• 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 PI or sub-investigator. 
• At sites processing blood for PBMCs isolation, approximately 24 mL of venous blood 
will be collected for future research. 
Note: This visit may be performed as a phone call assessment for sites not processing blood for 
PBMCs isolation. Study personnel will contact these subjects by phone to solicit any AE/SAEs 
and concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines). Based on the information collected, subjects may be asked to return to the clinic for 
evaluation. 


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8.2.5 Visit 06, Day 22, Clinic Visit 
(Window: Day 22+7 days post 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 phone call will be noted. 
• Concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines) will be recorded on the appropriate DCF. 
• All AE/SAEs will be recorded on the appropriate DCF. 
• 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 PI or sub-investigator. 
• Approximately 15 mL of venous blood will be collected for serological assays. 
Approximately 5 mL of this venous blood sample will be designated for future research. 
• At sites processing blood for PBMCs isolation, approximately 24 mL of venous blood 
will be collected for future research. 
8.2.6 Visit 07, Day 61, Safety Follow-up, Phone Call 
(Window: Day 61±7 days post study vaccination) 
Subjects will be contacted by phone to query for safety events and receipt of any non-study 
influenza vaccines. AEs limited to SAEs and MAAEs, including NOCMCs and PIMMCs, that 
have occurred since the previous clinic visit or phone call will be solicited. Based on the 
information collected, subjects may be asked to return to the clinic for evaluation. 
8.2.7 Visit 08, Day 91, Clinic Visit 
(Window: Day 91±14 days post 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 phone call will be noted. 
• Receipt of any non-study influenza vaccines will be recorded on the appropriate DCF. 


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• AEs limited to SAEs and MAAEs, including NOCMCs and PIMMCs, that have occurred 
since the previous clinic visit or phone call 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 PI or sub-investigator. 
• At sites processing blood for PBMCs isolation, approximately 56 mL of venous blood 
will be collected for future research. 
Note: This visit may be performed as a phone call assessment for sites not processing blood for 
PBMCs isolation. Study personnel will contact these subjects by phone to solicit receipt of any 
non-study influenza vaccines and AEs limited to SAEs and MAAEs, including NOCMCs and 
PIMMCs, that have occurred since the previous clinic visit or phone call. Based on the 
information collected, subjects may be asked to return to the clinic for evaluation. 
8.2.8 Visit 09, Day 121, Safety Follow-up, Phone Call 
(Window: Day 121±14 days post study vaccination) 
Subjects will be contacted by phone to query for safety events and receipt of any non-study 
influenza vaccines. AEs limited to SAEs and MAAEs, including NOCMCs and PIMMCs, that 
have occurred since the previous clinic visit or phone call will be solicited. Based on the 
information collected, subjects may be asked to return to the clinic for evaluation. 
8.2.9 Visit 10, Day 181, Clinic Visit 
(Window: Day 181±14 days post 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 phone call will be noted. 
• Receipt of any non-study influenza vaccines will be recorded on the appropriate DCF. 
• AEs limited to SAEs and MAAEs, including NOCMCs and PIMMCs, that have occurred 
since the previous clinic visit or phone call 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 


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a study clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as 
the site PI or sub-investigator. 
• Approximately 15 mL of venous blood will be collected for serological assays. 
Approximately 5 mL of this venous blood sample will be designated for future research. 
• At sites processing blood for PBMCs isolation, approximately 48 mL of venous blood 
will be collected for future research. 
8.3 
Final Visit 
8.3.1 Visit 11, Day 366, Safety Follow-up, Phone Call 
(Window: Day 366±14 days post study vaccination) 
Subjects will be contacted by phone to query for safety events. AEs limited to SAEs and 
MAAEs, including NOCMCs and PIMMCs, that have occurred since the previous clinic visit or 
phone call will be solicited. Based on the information collected, subjects may be asked to return 
to the clinic for evaluation. 
8.4 
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, 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 phone call will be noted. 
• Concomitant medications will be recorded on the appropriate DCF (if prior to 21 days 
after study vaccination). Receipt of any non-study influenza vaccines will also be 
recorded on the appropriate DCF (if within 180 days after study vaccination). 
• All AE/SAEs will be recorded on the appropriate DCF. AEs limited to SAEs and 
MAAEs, including NOCMCs and PIMMCs, that have occurred since the previous clinic 
visit or phone call will be solicited (if after 21 days after study vaccination). 
• Memory Aid information will be reviewed with subjects (if within 7 days after study 
vaccination). 


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• Vital signs, including oral temperature, pulse and BP, 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 PI or sub-investigator. 
• The study vaccination site will be examined (if within 7 days after study vaccination). 
• Post-administration reactogenicity assessments will be performed (if within 7 days after 
study vaccination). 
• Approximately 10 mL of venous blood will be collected for clinical safety labs (WBC, 
Hgb, PLT, ALT, T. Bili, Cr) to be performed by the central (clinical) laboratory (if within 
7 days after study vaccination). 
• Approximately 15 mL of venous blood will be collected for serological assays (if within 
21 days after study vaccination). Approximately 5 mL of this venous blood sample will 
be designated for future research. 
• At sites processing blood for PBMCs isolation, approximately 48 mL of venous blood 
will be collected for future research (if within 21 days after study vaccination). 
8.5 
Unscheduled Visit (if needed) 
An Unscheduled Visit 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, 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 phone call will be noted (if 
indicated). 
• Concomitant medications will be recorded on the appropriate DCF (if prior to 21 days 
after study vaccination). Receipt of any non-study influenza vaccines will also be 
recorded on the appropriate DCF (if within 180 days after study vaccination). 


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• All AE/SAEs will be recorded on the appropriate DCF. AEs limited to SAEs and 
MAAEs, including NOCMCs and PIMMCs, that have occurred since the previous clinic 
visit or phone call will be solicited (if after 21 days after study vaccination). 
• Memory Aid information will be reviewed with subjects (if within 7 days after study 
vaccination). 
• Vital signs, including oral temperature, pulse and BP, 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 PI or sub-investigator. 
• The study vaccination site will be examined (if within 7 days after study vaccination). 
• Post-administration reactogenicity assessments will be performed (if within 7 days after 
study vaccination). 
• Approximately 10 mL of venous blood will be collected for clinical safety labs (WBC, 
Hgb, PLT, ALT, T. Bili, Cr) to be performed by the central (clinical) laboratory (if 
indicated). 
• Approximately 15 mL of venous blood will be collected for serological assays (if within 
21 days after study vaccination). Approximately 5 mL of this venous blood sample will 
be designated for future research. 
• At sites processing blood for PBMCs isolation, approximately 48 mL of venous blood 
will be collected for future research (if within 21 days after study vaccination). 
 


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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 study vaccination through approximately 12 months 
after study vaccination. 
2. Solicited AEs – reactogenicity events occurring from the time of study vaccination 
through 7 days after study vaccination: 
a) Injection site reactions including pruritus, ecchymosis, erythema, induration/edema, 
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 study vaccination through 
approximately 7 days after 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 study vaccination through 
approximately 21 days after study vaccination. 
5. MAAEs, including NOCMCs and PIMMCs, occurring from the time of study vaccination 
through approximately 12 months after study vaccination. 
9.2 
Methods and Timing for Assessing, Recording and Analyzing Safety 
Parameters 
9.2.1 Adverse Events 
Adverse Event (AE): ICH E6 GCP 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. The FDA defines an AE as any untoward medical 
occurrence associated with the use of a drug in humans, whether or not considered drug related. 
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) 


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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. 
AEs, including solicited injection site and systemic (subjective and quantitative) reactions, not 
meeting the protocol-defined criteria for SAEs, will be recorded on the appropriate DCF and 
entered into the eCRF. Information to be collected for unsolicited non-serious AEs includes 
event description, date of onset, licensed study physician’s assessment of severity and 
relationship to study product or 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 PI or sub-investigator), date of resolution, seriousness, and outcome. AEs occurring 
during the trial-collection and reporting period will be documented appropriately regardless of 
relationship to study product. 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 assessed for severity and 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 DCF and entered into 
the eCRF. 
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. 
New-Onset Chronic Medical Conditions (NOCMCs): NOCMCs are defined as any new ICD-
10 diagnosis (10th revision of the International Statistical Classification of Diseases and Related 
Health Problems) that is applied to the subject during the course 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. 
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 Potentially Immune-Mediated Medical 
Conditions (PIMMCs). 


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Severity of Event: AEs will be assessed by a licensed study physician listed on the Form FDA 
1572 as the site PI or 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: 
• 
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 physician’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 
injection site and systemic (subjective and quantitative) reactions: 
 
 
 


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Table 4: 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 if 
pain medication is used, it 
is Over the Counter 
(OTC) and used for less 
than 24 hours 
Subject is aware of pain; 
there is interference with 
daily activity or OTC 
pain medication is used 
for more than 24 hours 
Subject is aware of pain, 
and it prevents daily 
activity or pain requires 
prescription medication 
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)/Edema 
(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 (hardness)/edema (swelling) as analyzed by measurement 
will be graded as follows: 
Table 5: Injection Site Reactogenicity Measurements 
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)/Edema 
(Swelling)* 
<20 mm 
20 mm – 50 mm 
>50 mm 
* Will not be used as halting criteria. 
 
 


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Table 6: 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 
* Not at injection site. 
Oral temperature# will be graded as follows: 
Table 7: Quantitative Systemic (Oral Temperature) 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 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 
Pulse and BP# will be graded as follows: 
 
 


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Table 8: Pulse and BP Adverse Event Grading 
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 
# Pulse and BP assessed on Day 1 prior to study vaccination will be considered as baseline. 
Clinical safety laboratory values# will be graded as follows: 
Table 9: 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 


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# Clinical safety laboratory evaluations assessed on Day 1 prior to 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 PI (or appropriate sub-investigator) or sponsor, it results in any of 
the following outcomes: 
• Death, 
• A life-threatening AE*, 
• Inpatient hospitalization or prolongation of existing hospitalization, 
• 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 PI 
(or appropriate sub-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 or alternate etiology (if not related 
to study product) by a licensed study physician listed on the Form FDA 1572 as the site 
PI or sub-investigator. 
• 
Recorded on the appropriate SAE form and entered into the eCRF. 


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• 
Followed through resolution by a licensed study physician listed on the Form FDA 1572 
as the site PI or sub-investigator. 
• 
Reviewed and evaluated by the Independent Safety Monitor (ISM) (as deemed 
necessary), DSMB (periodic review unless related), DMID, and IRB. 
9.2.5 Procedures to be Followed in the Event of Abnormal Laboratory Test Values or 
Abnormal Clinical Findings 
The site PI or appropriate sub-investigator is responsible for recording all AE/SAEs that are 
observed or reported during this trial, regardless of 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 5.1 and the protocol-specific MOP. 
9.3 
Reporting Procedures 
Solicited injection site and systemic reactogenicity events will be documented and reported from 
the time of study vaccination through 7 days after study vaccination. 
Clinical safety laboratory AEs will be documented and reported from the time of study 
vaccination through approximately 7 days after study vaccination. 
Unsolicited non-serious AEs will be documented and reported from the time of study vaccination 
through approximately 21 days after study vaccination. 
SAEs and MAAEs, including NOCMCs and PIMMCs, will be documented and reported from 
the time of study vaccination through approximately 12 months after 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: 
 
 
 


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DMID Pharmacovigilance Group 
Clinical Research Operations and Management Support (CROMS) 
6500 Rock Spring Dr. Suite 650 
Bethesda, MD 20817, USA 
SAE Hot Line: 1-800-537-9979 (US) or 1-301-897-1709 (outside US) 
SAE FAX: 1-800-275-7619 (US) or 1-301-897-1710 (outside US) 
SAE Email Address: PVG@dmidcroms.com 
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 subject safety and protocol conduct. 
At any time after completion of this trial, if the site PI or appropriate sub-investigator becomes 
aware of an SAE that is suspected to be related to study product, the site PI 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 PI 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 the 
FDA and all investigators (i.e., all participating VTEU site PIs to whom the sponsor is providing 
drug under its IND(s) or under any PI’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 the 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 the FDA, 
DMID will submit to the FDA any additional data or information that the agency deems 


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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 subjects will be recorded on the Pregnancy Report DCF. No study 
vaccination will be administered to a pregnant subject. If a subject becomes pregnant after 
receipt of study vaccine, with the subject’s permission, a venous blood sample for serological 
assays approximately 21 and 180 days after study vaccination will be obtained, and the subject 
will continue to be followed for safety for the duration of the prescribed safety follow-up period. 
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 study 
vaccination through approximately 21 days after study vaccination. 
SAEs and MAAEs, including NOCMCs and PIMMCs, will be collected, assessed and followed 
from the time of study vaccination through resolution even if this extends beyond the trial-
reporting period (approximately 12 months after 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 DCF and 
entered into the eCRF. 
9.5 
Halting Rules 
Additional enrollment and study interventions/administration of study products in this trial 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 that is 
considered related to study product administration. 


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• 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 an SAE after administration of study product that is considered 
related to study product. 
• 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 study vaccination, any of the following occurs: 
• 7% or more of subjects (with a minimum of 3 subjects) who received a dose of study 
vaccine experience the same severe (Grade 3) study vaccine-related injection site 
reaction. Ecchymosis, erythema and induration (hardness)/edema (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 a dose of study 
vaccine 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 a dose of study 
vaccine 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 a dose of study 
vaccine 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. 


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If any of the halting rules are met following any subject receipt of study vaccination, then this 
trial will not continue with the remaining enrollments 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 products during this 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) 
An ISM is a physician with relevant expertise whose primary responsibility is to provide to 
DMID an independent safety assessment in a timely fashion. This is a voluntary position that 
does not receive payment. The ISM must meet the requirements of the NIAID Conflict of 
Interest (COI) policy. 
For this clinical trial an ISM is not required. However, at each participating VTEU site, upon 
DMID Medical Monitor request, the site PI will identify a physician with relevant expertise, to 
act as a Secondary Medical Assessor (SMA). The SMA will examine a subject and/or medical 
records and provide to DMID a medical assessment (or second medical opinion) of the safety 
event in question. The site PI or appropriate sub-investigator will send to the DMID Medical 
Monitor, a summary of the event and include the site PI or appropriate sub-investigator and SMA 
assessments. 
Note: In the case that DMID has requested this type of evaluation multiple times, DMID may 
request the participating VTEU site(s) identify an ISM to assist DMID with safety oversight, and 
then the below requirements will apply. 
The ISM: 
• 
Is in close proximity to the study site and has the authority and ability to readily access 
subject records in real time. 
• 
May be a member of the participating VTEU site’s staff, but preferably be from a 
different organizational group within the institution. 
• 
Should not be in a direct supervisory relationship with the site PI. 


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• 
Should have no direct involvement in the conduct of the study. 
The ISM will: 
• 
Sign a COI certification at the time he/she is asked to participate and provide updates to 
this information as needed. 
• 
Receive reports of SAEs from the site PI or appropriate sub-investigator and will be 
notified by email when DMID is notified of the SAE. 
• 
Evaluate the SAE and report his/her clinical assessment to DMID in a timely manner. 
• 
Communicate with the site PI or appropriate sub-investigator at the participating VTEU 
site as needed. 
• 
Review additional safety related events at the request of DMID. 
• 
Provide additional information to DMID and/or the DSMB by teleconference as 
requested. 
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 COI 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. 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 
subject, clinical, safety, reactogenicity, and immunogenicity data. Reports may include 
enrollment and demographic information, medical history, concomitant medications, physical 
assessments, clinical laboratory values, dosing compliance, solicited and unsolicited AE/SAEs, 
and 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: 
• Data review for safety at trial-specific time frames; at least annually. 


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• Electronic review when 8-day reactogenicity and clinical safety laboratory data following 
study vaccination is available for 25% of study subjects. 
• Data review when 8-day reactogenicity and clinical safety laboratory data following 
study vaccination is available for 75% of study subjects. 
• 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. The DMID Medical Monitor is empowered to stop enrollment and study 
vaccinations if AEs that meet the halting criteria are reported. 
• 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 
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. 
 


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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 interventions/administration of study products, and data collection processes 
are of high quality and meet sponsor and ICH E6 GCP guidelines and applicable federal 
regulations, and that this trial is conducted in accordance with the protocol, protocol-specific 
MOP and applicable sponsor SOPs. DMID, the sponsoring agency, or its designee will conduct 
site-monitoring visits as detailed in the clinical monitoring plan. DMID-designated clinical 
monitors will verify that this trial is conducted and data are generated, documented (recorded) 
and reported in compliance with the protocol, ICH E6 GCP guidelines and applicable regulatory 
requirements. Clinical monitoring reports will be submitted to DMID. 
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, ICFs, 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 PIs 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 the safety, reactogenicity, and immunogenicity of a 
single boosting dose of 2017 A/H7N9 IIV with or without AS03 adjuvant in subjects who 
received 2013 A/H7N9 IIV in previous trials (DMID Protocols 13-0032 and 13-0033) and 
subjects who are A/H7 IIV-naïve. These treatment arms are included to allow evaluation of the 
priming effect of the 2013 A/H7N9 IIV given with/without adjuvant to enhance the immune 
response to the 2017 A/H7N9 IIV. Additional goals are to investigate novel methods for 
identifying and assessing alternative serological correlates of protection against influenza 
infection. 
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 outlined 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, 19 to 70 
years of age, inclusive, who are in good health and meet all eligibility criteria. The subjects will 
be recruited from the general population at each of 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, 
7 VTEUs recruited 388 healthy subjects, 19 to 64 years of age, in 14 weeks. Prior experience 
suggests approximately to 3% of subjects may be excluded from the per protocol (PP) analysis 
for the primary immunogenicity outcome either because they were lost-to-follow-up, or because 
they had a protocol deviation requiring their exclusion from the PP analysis. 
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 study vaccination. The 
second segment consists of a 6-month immunogenicity assessment and follow-up safety 
assessments through approximately 12 months after study vaccination. 
11.4.3 Sample Size 
This study is planned to enroll up to 420 subjects. The majority of subjects will be recruited from 
the population of subjects who received the 2013 A/H7N9 IIV in DMID Protocols 13-0032 and 
13-0033. The sample size for this study was selected using estimates of recruitment based on the 
number of subjects completing these historical protocols by 2013 A/H7N9 IIV vaccination 
history (summarized in Table 10). 
 
 
 


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Table 10: Previously Primed Subjects For Potential Enrollment in 17-0090 
17-0090 Study 
Strata 
2013 
A/H7N9 IIV 
Protocol 
Treatment 
Arms 
Dose 
1 
Dose 
2 
Completed 
All Visits 
Able to 
recruit 
50% 
Completers 
Able to 
recruit 
25% 
Completers 
One or two 
doses 2013 
A/H7N9 IIV 
with MF59 
13-0032 
Treatment 
Arms 1-3 
13-0033 
Treatment 
Arm 8 
396 
387 
385 
192 
96 
One or two 
doses 2013 
A/H7N9 IIV 
with AS03 
13-0033 
Treatment 
Arms 1-3 
291 
278 
279 
137 
70 
One or two 
doses 2013 
A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
13-0032 
Treatment 
Arms 6-7 
13-0033 
Treatment 
Arms 9-10 
396 
383 
383 
191 
95 
2013 A/H7N9 
IIV + MF59 or 
AS03 (1st) then 
2013 A/H7N9 
IIV 15 mcg (2nd) 
13-0032 
Treatment 
Arm 4 
13-0033 
Treatment 
Arm 4 
199 
190 
193 
96 
48 


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While this study is not designed to test any specific null hypothesis, the following illustrates the 
precision and power that are available for select estimates and comparisons of interest. 
 
 


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Table 12 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 treatment arms (N=30, 50), in all subjects receiving adjuvant (N=210), or in the trial as a 
whole (N=420). 
Table 11: Power (%) to Detect Safety Events 
Event 
Frequency 
N=30 
N=50 
N=210 N=420 
≥10% 
Very Common 
95 
>99 
>99 
>99 
≥1% 
Common 
26 
39 
87 
98 
≥0.1% 
Uncommon 
2 
4 
18 
34 
≥0.01% 
Rare 
<1 
<1 
2 
4 
Binomial confidence intervals (CI) are widest (have the least precision) when the response rate is 
50%.  
 


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Table 12 is presented to indicate the worst-case scenario for precision of observed exact 
(Clopper-Pearson) binomial confidence intervals. 
 
 
 


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Table 12: Precision of Binomial Confidence Intervals 
N 
95% CI 
30 
31-69 
50 
35-65 
210 
43-57 
420 
45-55 
Table 13 illustrates the minimum detectable differences in the proportion of subjects responding 
(e.g. attaining seroconversion or a titer ≥1:40) between any two treatment arms (N=30 or 50) 
using a two-sided Likelihood Ratio Test and alpha = 0.05.  
From previous experience with single dose studies, it is assumed that up to 3% of subjects will 
be excluded from the per protocol analysis with minimal effect on these calculations. 
Seroconversion rates of 10% to 90% are considered. 
Table 13: Minimum Detectable Difference in Proportion Responders 
N per Treatment 
Arm 
Proportion 
Responders in 
Comparator 
Group A 
80% Power 
Minimal Detectable Difference 
Proportion 
Responders 
in 
Comparator 
Group B 
N=30 
0.10 
0.29 
0.39 
0.20 
0.34 
0.54 
0.30 
0.35 
0.65 


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0.40 
0.35 
0.75 
0.50 
0.33 
0.83 
0.60 
0.30 
0.90 
0.70 
0.25 
0.95 
0.80 
0.19 
0.99 
0.90 
0.10 
>0.99 
N=50 
0.10 
0.22 
0.32 
0.20 
0.26 
0.46 
0.30 
0.27 
0.57 
0.40 
0.27 
0.67 
0.50 
0.27 
0.77 
0.60 
0.25 
0.85 
0.70 
0.22 
0.92 
0.80 
0.17 
0.96 
0.90 
0.10 
>0.99 


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11.5 
Planned Interim Analyses 
A DSMB will be convened by DMID to review study progress and subject, clinical, safety, 
reactogenicity, and immunogenicity data as described in Section 9.6.2. 
A set of “topline” immunogenicity and safety tables produced on an expedited timeline will be 
prepared as described in Section 11.6; though this report will be released while subjects remain 
in this 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 this trial. If 
this occurs, immunogenicity data will be analyzed as results are available from Southern 
Research. 
Interim analyses will be used only 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. 
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 trial-specific time frames 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. 
The interim safety reports generated for the DSMB are not intended to be published; they will be 
used only for informing emergency preparedness. 
Additionally, this trial will be monitored to determine if any of the halting rules described in 
Section 9.5 are met. 


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11.5.2 Interim Immunogenicity Review 
Should emergent public health needs dictate interim immunogenicity review, immune responses 
will be summarized in terms of strain-specific 2013 and 2017 A/H7N9 HAI and Neut antibody 
titers and the relationship to adjuvant use. It is anticipated that all analyses will be carried out in 
parallel for both assays, but reports may be prepared separately for HAIs 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 
GMTs, along with corresponding 95% CIs. No formal hypothesis testing will be included in the 
interim analysis, and interim results will not have impact on conduct of this trial. 
Any immunogenicity reports would be provided by the SDCC to the DMID Scientific Lead, 
DMID Clinical Project Manager and 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. 
There is no plan to halt this trial prior to full enrollment and completion of all follow-up visits 
based on any interim immunogenicity results. 
11.6 
Final Analysis Plan 
Clinical, safety and reactogenicity data through approximately 180 days after study vaccination 
will represent the primary clinical database for this trial. Once the last subject completes the visit 
that occurs approximately 180 days after study vaccination and all HAI and Neut results are 
received, a “topline” subset of the immunogenicity and safety tables will be provided to DMID 
on an expedited timeline. These analyses may be made available to the sponsor for planning 
subsequent trials and to the lead PI 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 and immunogenicity follow-up at the time of these analyses, blinded site 
investigators and DMID Medical Monitors not involved in the analysis, publication or clinical 
study report (CSR) preparation will be responsible for assessing SAEs and MAAEs, including 
NOCMCs and PIMMCs, until all subjects have completed the final follow-up visit. All analyses 
of data included in the topline tables for early release will be considered the final analysis of 
these data, and also included in the final CSR. 
Analysis of exploratory immunogenicity endpoints, including additional serological assays, may 
be performed and released as the data are available from the research laboratories. 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. 
A formal statistical analysis plan (SAP) will be developed and finalized prior to unblinding for 
any analysis, which defines the analyses to be included in the topline tables and final CSR. 
11.6.1 Analysis Populations 
The Safety Analysis population includes all subjects who received study vaccine. 
The modified intent-to-treat (mITT) population includes all subjects who received study vaccine 
and contributed both pre- and at least one post-study vaccination venous blood samples for HAI 
and Neut antibody assays for which valid results were reported. For analyses using the mITT 
population, subjects will be grouped based on their randomized treatment arm. 
The 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: 
• Receipt of non-study licensed, live vaccine within 30 days before or after study 
vaccination, 
• Receipt of non-study licensed, inactivated vaccine within 14 days before or after 
study vaccination, 
• Receipt of immunosuppressive therapy (e.g., corticosteroids) within 30 days 
before or after 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 vaccination 
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. 


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Solicited AEs will be summarized by severity for each day after study vaccination (Days 1-8 
post 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 CIs, to summarize the proportion of subjects reporting each symptom, any injection site 
symptom and any systemic symptom. The proportion of subjects reporting symptoms may be 
compared between treatment arms using Chi-square or Fisher’s exact test. 
Unsolicited AEs will be coded by Medical Dictionary for Regulatory Activities (MedDRA) for 
preferred term (PT) and system organ class (SOC). The numbers of SAEs and 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 PT 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 PT and SOC, cross-tabulated by severity and relationship to study 
product. Additionally, the proportion of subjects and exact 95% CIs 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 2013 and 2017 A/H7N9 HAI and Neut antibody 
titers will be summarized by treatment arm at each time point. Analyses will include number and 
percentage of subjects with a titer ≥1:40, number and percentage of subjects achieving 
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 antibody titer), 
and GMTs along with corresponding 95% CIs. 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, BMI, and prior receipt of seasonal or non-study pandemic influenza 
vaccine(s), and these covariates may be considered statistical modeling. As an exploratory 
analysis, models may be developed to evaluate the relationship between use of adjuvant and 


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prime and/or boost regimens with the elicited immune response. For example, logistic regression 
may be used to examine the relationship of proportion of responders with adjuvant use in the 
prime and/or boost regimens and available covariates may be considered for inclusion in the 
model. 
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 2013 and 2017 
A/H7N9 responses and association with adjuvant use in the prime and/or boost regimens. 
N9 NA-specific serum antibody assays are in development. N9 NA-specific serum antibody 
responses, in at least a subset of samples, will be assessed at baseline and approximately 7, 21 
and 180 days after study vaccination. For each time point, summaries may include number and 
percentage of subjects with detectable N9 NA-specific serum antibody responses (to be defined 
in SAP following assay development and selection) and GMTs along with corresponding 95% 
CIs. N9 NA-specific serum antibody responses and GMTs will be summarized stratified by use 
of adjuvant in prime and/or boost regimens, and statistical modeling may be used to examine the 
relationship of NA response with the inclusion of adjuvant in these regimens and associations 
with covariates such as prior receipt of influenza vaccine. 
HA stem-specific antibody responses will be assessed at baseline as well as 7, 21 and 180 days 
after study vaccination, in at least a subset of samples, and will be summarized by treatment arm 
at each time point. Analyses will include GMTs with corresponding 95% CIs. 
In addition, correlation of N9 NA-specific serum antibody responses with HAI and Neut or HA 
stem-specific antibody titers will be evaluated, and plots such as reverse cumulative distributions 
or longitudinal presentations of GMTs will be presented. 
Further immunogenicity testing and/or analyses may be carried out in the future based upon 
subjects’ prior receipt of non-seasonal influenza vaccine, 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 
clinical trial, in compliance with ICH E6 GCP Section 4.9 and regulatory and institutional 
requirements for the protection of confidentiality of subjects. Each participating VTEU site will 
permit the study monitor or other authorized representatives of DMID as well as governmental 
regulatory agencies, such as the FDA, 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 this clinical 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 clinical 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 
(and its subcontractors) is responsible for conducting routine quality assurance (QA) and quality 
control (QC) activities to internally monitor study progress and protocol compliance. Each site PI 
will provide direct access to all study-related sites, source data/DCFs and reports for the purpose 
of monitoring and auditing by the sponsor, and inspection by local and regulatory authorities. 
Each site PI will ensure all study personnel are appropriately trained and applicable 
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 PIs 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 (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 21 CFR 56, as 
applicable. The site PIs will also ensure conformity with ICH E6 GCP and applicable federal 
regulations, guidance and guidelines for GCP and Clinical Trials with humans. 
14.2 
Institutional Review Board (IRB) 
Each institution engaged in this research will hold a current Federalwide Assurance (FWA) 
issued by the Office for Human Research Protections (OHRP) for federally funded research. The 
IRB must be registered with OHRP [OHRP-only or OHRP/FDA] as applicable to the research. 
The IRB FWA number will be provided to DMID. 
Each site PI will obtain IRB approval for this protocol to be conducted at his/her research site(s), 
and send supporting documentation to DMID before initiating recruitment of subjects. The site 
PI will submit applicable information to the IRB on which it relies for the review, to conduct the 
review in accordance with 45 CFR 46, ICH E6 GCP guidelines, and as applicable, 21 CFR 56 
(Institutional Review Boards), 21 CFR 50 (Protection of Human Subjects), and other federal, 
state and local regulations and guidance. DMID must receive the documentation that verifies 
IRB approval for this protocol, associated informed consent documents, and upon request, any 
recruitment material and handouts or surveys intended for the subjects, prior to the recruitment 
and enrollment of subjects. 
Any amendments to the protocol or consent materials will be approved by the IRB before they 
are implemented. IRB review and approval will occur at least annually throughout the enrollment 
and follow-up of subjects, and may cease if annual review is no longer required by applicable 
regulations. The site PI will notify the IRB of protocol deviations and reportable SAEs in 
accordance with IRB requirements. 
14.3 
Informed Consent Process 
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 


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are performed, informed consent will be obtained and documented. Subjects will receive a 
concise and focused presentation of key information about the trial, verbally and with a written 
ICF. The explanation will be organized, and presented in lay terminology and language that 
facilitates understanding why one might or might not want to participate. The ICF must not 
include any exculpatory statements. 
The site PIs or their designees will describe the protocol to potential subjects face-to-face. The 
key information about the purpose of the trial, the procedures and experimental aspects of the 
trial, risks and discomforts, any expected benefits to the subject, and alternative treatment will be 
presented first to the subject. 
Subjects will also receive an explanation that the trial involves research and a detailed summary 
of the proposed study procedures and study interventions/study products. This will include 
aspects of the trial that are experimental, the probability for random assignment to treatment 
arms, any expected benefits, all possible risks (including a statement that the particular treatment 
or procedure may involve risks to the subject or to the embryo or fetus, if the subject is or may 
become pregnant, that are currently unforeseeable), the expected duration of the subject’s 
participation in the trial, alternative treatment/procedures that may be available, and the 
important potential benefits and risks of these available alternative treatment/procedures. 
Subjects will be informed that they will be notified in a timely manner if information becomes 
available that may be relevant to their willingness to continue participation in the trial. Subjects 
will receive an explanation as to whether any compensation and any medical treatments are 
available if injury occurs, and, if so, what they consist of or where further information may be 
obtained. Subjects will be informed of the anticipated financial expenses, if any, to the subject 
for participating in the trial, as well as any anticipated prorated payments, if any, to the subject 
for participating in the trial. They will be informed of whom to contact (e.g., the site PI) for 
answers to any questions relating to the research project. 
Information will also include the foreseeable circumstances and/or reasons under which the 
subject’s participation in the trial may be terminated. The subjects will be informed that 
participation is voluntary and that they are free to withdraw from the study for any reason at any 
time without penalty or loss of benefits to which the subject is otherwise entitled. 
The extent of the confidentiality of the subjects’ records will be defined, and subjects will be 
informed that applicable data protection legislation will be followed. Subjects will be informed 
that the monitors, auditors, IRB, NIAID, and regulatory authorities will be granted direct access 
to the subject’s original medical records for verification of trial procedures and/or data without 
violating the confidentiality of the subject, to the extent permitted by the applicable laws and 
regulations, and that, by signing a written ICF, the subject is authorizing such access. 


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Subjects will be informed that records identifying the subject will be kept confidential and, to the 
extent permitted by the applicable laws and/or regulations, will not be made publicly available 
and, if the results of the trial are published, the subject’s identity will remain confidential. 
Subjects will be informed whether private information collected from this research and/or 
samples/specimens will be used for additional research, even if identifiers are removed. 
Subjects will be allowed sufficient time to consider participation in the trial, and have the 
opportunity to discuss the trial with their family, friends or legally authorized representative, or 
think about it prior to agreeing to participate. 
ICFs will be IRB-approved and subjects will be asked to read and review the ICF. Subjects must 
sign the ICF prior to starting any study procedures being done specifically for the trial. 
Once signed, a copy of the ICF will be given to the subjects for their records. The subject(s) may 
withdraw consent at any time throughout the course of the trial. The rights and welfare of the 
subjects will be protected by emphasizing to them that the quality of their medical care will not 
be adversely affected if they decline to participate in or withdraw from the trial. 
New information that significantly impacts the subject’s risk of receiving the study 
interventions/study products will be communicated by the site PIs or their designees to the 
subjects who consent to participate in the trial in accordance with IRB requirements. The ICF 
will be updated and subjects will be re-consented in accordance with IRB requirements, if 
necessary. Subjects will be given a copy of all ICFs that they sign. 
Study personnel may employ IRB-approved recruitment efforts prior to obtaining study consent 
if a patient-specific screening consent is on record or if the IRB has agreed that chart review is 
allowed without a fully executed screening consent. In cases where there is not a patient-specific 
screening consent on record, Clinical staff may pre-screen via chart review and refer potential 
subjects to the Research staff. Research staff would obtain written consent per the standard 
informed consent process before conducting protocol-specific screening activities. 
14.4 
Exclusion of Women, Minorities and Children (Special Populations) 
This trial will be inclusive of all subjects, 19 to 70 years of age, 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 [74]. 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 A/H7N9 IIV with or without AS03 adjuvant poses any risks to an 
unborn child. As of November 22, 2015 (per the GSK AS03 Adjuvant Investigator’s Brochure 
dated February 2016), 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 has passed since the last menses if menopausal must 
agree to practice highly effective contraception that may include 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 study vaccination, barrier methods such as condoms or diaphragms/cervical cap with 
spermicide, 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 vaccine exposure and agree to practice 
highly effective contraception for the duration of study vaccine 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 PIs, other study personnel, the sponsor, 
and their agents. This confidentiality includes documentation, investigation data, subject’s 
clinical information, and all other information generated during participation in this trial. No 
information concerning this trial or the data generated from this trial will be released to any 
unauthorized third party without prior written approval of the subject and DMID. 
Subject confidentiality will be maintained when trial results are published or discussed in 
conferences, and is extended to cover testing of samples/specimens. The study monitor or other 
authorized representatives of DMID as well as governmental regulatory agencies, such as the 
FDA, may inspect all documents and records required to be maintained by the site PIs. This 


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includes, but is not limited to, medical records (office, clinic or hospital) and pharmacy records 
for the subjects in this trial. The participating VTEU sites will permit access to such records. 
All records will be kept locked and all computer entry and networking programs will be carried 
out with coded numbers only and with password-protected systems. All non-clinical 
samples/specimens, evaluation forms, reports, and other records that leave the site will be 
identified only by a coded number and will not be identified by the subject’s name. 
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 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 US 
Government that is used for auditing or evaluation of federally funded projects, like this trial, or 
for information that must be released in order to meet the requirements of the 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 prematurely terminated by the sponsor, any regulatory authority, the site PI, or 
appropriate sub-investigator for any reason, the site PI or appropriate sub-investigator will 
promptly inform the subjects and assure appropriate therapy or follow-up for the subjects, as 
necessary. The site PI or appropriate sub-investigator will provide a detailed written explanation 
of the termination to the IRB. If any subject’s private information will continue to be collected 
for this trial, the IRB must approve an ICF with the study procedures, any risks and discomforts 
as well as applicable elements, and the site PI or designee will re-consent the subjects as 
approved by the IRB. 


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If this trial is discontinued, subjects, who have signed the ICF, 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 the research tests, study procedures/evaluations or study vaccine 
while taking part in this trial. 
Subjects may be compensated for their participation in this trial. Compensation will be in 
accordance with local IRB requirements, and subject to local IRB approval. 
If it is determined by the participating VTEU site and the site PI that an injury occurred to a 
subject as a direct result of the tests or treatments that are done for this trial, then 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 NIAID, NIH or the participating VTEU site for any injury suffered due to 
participation in this trial. 
For this protocol, the study products (2017 A/H7N9 IIV manufactured by Sanofi Pasteur and 
AS03 adjuvant manufactured by GSK) are covered under the PREP Act, as described in Section 
2.1.1. 
14.8 
Future Use of Stored Specimens 
Subjects who agree to participate in this trial will have venous blood collected for ESR and 
clinical safety laboratory evaluations, serological assays and future research. 
Residual samples/specimens are those that are left over after protocol-specified testing for 
serological assays and this trial have been completed. Any remaining (residual) specimens 
(serum) derived from venous blood samples collected for serological assays will be kept for 
possible use in future research studies, such as examining additional immunological assessments 
or testing for antibodies against other viruses or bacteria. Residual specimens for future research 
use will be stored indefinitely at a central clinical storage facility and may be shared for purposes 
other than PP analysis with investigators at the participating VTEU site and with other 
investigators at other institutions once the CSR has been finalized. An IRB will review future 
research prior to the use of identifiable specimens or data. 


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Additional venous blood samples for serum, plasma and PBMC specimens will be collected 
during this trial specifically for the purpose of future research, including, but not limited to, 
cellular immunology assays, detailed systems biology analyses, antibody epitope mapping, B and 
T cell repertoire determination, non-traditional immune assay development, assessing innate 
immune factors, and the ability of A/H7 study vaccine-induced antibodies to cross-react with 
other influenza viruses. These samples/specimens might be used in new or different 
immunological laboratory tests, to provide information for the development of new vaccines, or 
for the studies of influenza or other infections. Samples/specimens collected during this trial 
specifically for the purpose of future research will be stored indefinitely at a central clinical 
storage facility and may be shared with investigators at the participating VTEU site and with 
other investigators at other institutions. An IRB will review future research prior to the use of 
identifiable specimens or data. 
Residual specimens will be available upon the completion of this trial; however, 
samples/specimens collected during this trial specifically for the purpose of future research may 
be requested from DMID and shipped from the DMID CMS at any time. 
There are no benefits to subjects in the collection, storage and future research use of their 
samples/specimens. Future research tests may benefit others by leading to new approaches in the 
development of vaccines or treatments for influenza. Future research use samples/specimens 
(residual specimens and samples/specimens collected during this trial specifically for the purpose 
of future research) will not be sold or used directly for production of any commercial product. 
Each sample/specimen will be encoded (labeled) only with a barcode and a unique tracking 
number to protect subject confidentiality. Reports from future research studies performed using 
subjects’ samples/specimens will NOT be kept in their health records and results will not be 
shared with subjects. 
Subjects will not be given the option to decide if they want their residual specimens to be used 
for future research or have these specimens destroyed at the end of this trial. Subjects will be 
asked to consent to the future research use of residual specimens as a condition of their study 
participation. 
Subjects will not be given the option to decide if they want their samples/specimens collected 
during this trial specifically for the purpose of future research to be used for future research or 
have these samples/specimens destroyed at the end of this trial. These samples/specimens are 
protocol-required; thus, subjects will be asked to consent to the future research use of these 
samples/specimens as a condition of their study participation. 
By signing a written ICF for this trial, subjects agree to the collection, storage and future 
research use of their samples/specimens (residual specimens and samples/specimens collected 
during this trial specifically for the purpose of future research). 


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After all subjects had enrolled, it was determined that genetic testing may be performed on 
residual specimens and samples/specimens collected during this trial specifically for the purpose 
of future use, under a secondary research protocol. Secondary research is research that is not part 
of this trial and will be performed in the future. Subjects will be informed and asked for their 
consent to use their residual specimens and samples/specimens collected during this trial 
specifically for the purpose of future research and information for genetic testing for “secondary 
research”. Genetic testing could include transcriptomics, whole genome or exome sequencing, or 
other types of genetic testing. This could contribute to identifying genetic factors involved in 
vaccine responses. Genetic testing results (data) may be shared broadly with other researchers 
but will not be shared with subjects. Individual results will be stored indefinitely in an NIH 
restricted-access database, and a summary of results may be placed in an unrestricted (open) 
database. 
The samples/specimens will be labeled as above for storage. The genetic data in the NIH 
database will be coded in such a way that information will be considered de-identified. Subjects 
will be informed of the risks, including potential for re-identification and possible harm from the 
mis-use of data, however, NIH will require researchers to not re-identify the subjects. 
Subjects will have the right to withdraw consent for the use of their samples/specimens and/or 
data without penalty at any time. Samples/specimens and data that have already been used for 
secondary research may not be able to be withdrawn. 
"Written", or "signed", refers to the use of or writing on a paper or an electronic ICF. Re-consent 
(revised or separate consent form) for secondary research using samples/specimens and 
information, such as for genetic testing, may use paper or electronic ICFs to obtain the subject’s 
written consent. The subject will have a discussion with study staff, who is able to answer the 
subject’s questions, including if re-consent is obtained off-site. A paper copy of the signed ICF 
will be given to the subject in person or mailed. 
 


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15 
DATA HANDLING AND RECORD KEEPING 
The site PIs are responsible to ensure the accuracy, completeness, legibility, and timeliness of the 
data reported. 
DCFs will be derived from the eCRF and provided by the SDCC to record and maintain data for 
each subject enrolled in this trial. All DCFs 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 DCFs should be consistent with the DCFs or the 
discrepancies should be explained. 
The sponsor and/or its designee will provide guidance to the site PIs and other study personnel 
on making corrections to the DCFs and eCRF. 
15.1 
Data Management Responsibilities 
All DCFs 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 
DCF, assessed for severity and relationship, and reviewed by the site PI 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 PI. During this trial, the site PIs 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 


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range checks, to identify data that appear inconsistent, incomplete or inaccurate. Clinical and 
reactogenicity data will be entered directly from the DCFs completed by the study personnel. 
15.3 
Types of Data 
Data for this trial will include clinical, safety and outcome measures (e.g., clinical laboratory 
values, and reactogenicity and immunogenicity data). 
15.4 
Timing/Reports 
Clinical, safety and reactogenicity data through approximately 180 days after study vaccination 
will represent the primary clinical database for this trial. Once the last subject completes the visit 
that occurs approximately 180 days after study vaccination and all HAI and Neut results are 
received, a “topline” subset of the immunogenicity and safety tables will be provided to DMID 
on an expedited timeline. These analyses may be made available to the sponsor for planning 
subsequent trials and to the lead PI 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 and immunogenicity follow-up at the time of these analyses, blinded site 
investigators and DMID Medical Monitors not involved in the analysis, publication or clinical 
study report (CSR) preparation will be responsible for assessing SAEs and MAAEs, including 
NOCMCs and PIMMCs, until all subjects have completed the final follow-up visit. All analyses 
of data included in the topline tables for early release will be considered the final analysis of 
these data, and also included in the final CSR. 
Analysis of exploratory immunogenicity endpoints, including additional serological assays, may 
be performed and released as the data are available from the research laboratories. 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. 
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 assignment. In this regard, the participating VTEU sites requesting such information to 
share with subjects must do so in accordance with IRB requirements. 


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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. These documents will be retained for a longer 
period, however, if required by local regulations. ICFs for future research use will be maintained 
as long as the sample/specimen exists. 
No records will be destroyed without the written consent of the sponsor. It is the responsibility of 
the sponsor to inform the site PI when these documents no longer need to be retained. The 
participating VTEU sites must contact DMID for authorization prior to the destruction of any 
study records. 
15.6 
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 PI or 
other study personnel. As a result of protocol deviations, corrective actions are to be developed 
by the site and implemented promptly. 
These practices are consistent with ICH E6 GCP guidelines: 
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 PI and other study personnel to use continuous vigilance to 
identify and report protocol deviations within five working days of identification of the protocol 
deviation, or within five working days of the scheduled protocol-required activity. Protocol 
deviations must be promptly reported to DMID, via the SDCC’s AdvantageEDCSM. 
Protocol deviations, as defined above, must be addressed on the appropriate DCF. A completed 
copy of the Protocol Deviation DCF must be maintained in the regulatory file as well as in the 
subject’s chart. Protocol deviations must be sent to the IRB in accordance with IRB 
requirements. The site PI and other study personnel are responsible for knowing and adhering to 
IRB requirements. 


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16 
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 all 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 clinical trial, the responsible party is DMID which will register this 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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17 
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35. 
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. 
36. 
Vogel, F.R., et al., Emulsion-based adjuvants for influenza vaccines. Expert Rev 
Vaccines, 2009. 8(4): p. 483-92. 
37. 
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. 
38. 
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. 
39. 
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). 
40. 
Force, N.N.T., Increased risk of narcolepsy observed also among adults vaccinated with 
Pandemrix in Finland N.I.f.H.a.W.T. Finland, Editor. 2013. 
41. 
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. 
42. 
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. 
43. 
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. 
44. 
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. 
45. 
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. 
46. 
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. 
47. 
El Sahly, H.M. and D.N. NIH, 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. 
48. 
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. 
49. 
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. 
50. 
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. 


DMID Protocol 17-0090 
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18 December 2019 
 
103 
51. 
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. 
52. 
Lee, Y.J., et al., Novel reassortant influenza A(H5N8) viruses, South Korea, 2014. Emerg 
Infect Dis, 2014. 20(6): p. 1087-9. 
53. 
Wu, H., et al., Novel reassortant influenza A(H5N8) viruses in domestic ducks, eastern 
China. Emerg Infect Dis, 2014. 20(8): p. 1315-8. 
54. 
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. 
55. 
Human infection with avian influenza A(H7N9) virus – China: 07 December 2017. WHO  
Emergencies preparedness, response, 2017. 
56. 
Analysis of recent scientific information on avian influenza A(H7N9) virus. WHO  
Influenza Update, 2017. 
57. 
Zhou, J., et al., Biological features of novel avian influenza A (H7N9) virus. Nature, 
2013. 499(7459): p. 500-3. 
58. 
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. 
59. 
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. 
60. 
Belshe, R.B., et al., Safety and immunogenicity of influenza A H5 subunit vaccines: effect 
of vaccine schedule and antigenic variant. J Infect Dis, 2011. 203(5): p. 666-73. 
61. 
Goji, N.A., et al., Immune responses of healthy subjects to a single dose of intramuscular 
inactivated influenza A/Vietnam/1203/2004 (H5N1) vaccine after priming with an 
antigenic variant. J Infect Dis, 2008. 198(5): p. 635-41. 
62. 
Gillard, P., et al., Long-term booster schedules with AS03A-adjuvanted heterologous 
H5N1 vaccines induces rapid and broad immune responses in Asian adults. BMC Infect 
Dis, 2014. 14: p. 142. 
63. 
Langley, J.M., et al., Immunogenicity of heterologous H5N1 influenza booster 
vaccination 6 or 18 months after primary vaccination in adults: a randomized controlled 
clinical trial. Vaccine, 2015. 33(4): p. 559-67. 
64. 
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. 
65. 
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. 
66. 
Haber, P., et al., Guillain-Barre syndrome following influenza vaccination. JAMA, 2004. 
292(20): p. 2478-81. 
67. 
De Wals, P., et al., Risk of Guillain-Barre syndrome following H1N1 influenza 
vaccination in Quebec. JAMA, 2012. 308(2): p. 175-81. 
68. 
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. 
69. 
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. 


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104 
70. 
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. 
71. 
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. 
72. 
Dodd, C.N., et al., International collaboration to assess the risk of Guillain Barre 
Syndrome following Influenza A (H1N1) 2009 monovalent vaccines. Vaccine, 2013. 
31(40): p. 4448-58. 
73. 
Sullivan, S.S., Narcolepsy in adolescents. Adolesc Med State Art Rev, 2010. 21(3): p. 
542-55, x-xi. 
74. 
CDC, Recommended Immunizations for Adults: By Age. 2017. 
 
 
 


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105 
Appendices 
Appendix A: Schedule of Study Procedures and Evaluations 
Appendix B: List of Potentially Immune-Mediated Medical Conditions (PIMMCs) 
 
 




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+ May be performed as phone call assessment for sites not processing blood for PBMCs isolation. 
**Phone call assessment. 
∞ Prior to study procedures. 
¬ Review/confirm information or activity in subjects previously consented and screened. 
† Prior to study vaccination. 
* Not required if done at the optional screening visit. 
1 Review results of ESR or clinical safety laboratory evaluations. 
@ Complete medical history will be obtained by interview of subjects at the screening visit (optional) or on Day 1 prior to study vaccination, and interim medical 
history will be obtained by interview of subjects at follow-up clinic visits after study vaccination. 
ς Concomitant medications limited to non-study influenza vaccines after Visit 06. 
% Subjects must not eat or drink anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
$ Vital signs assessed on Day 1 prior to study vaccination will be considered as baseline. 
! May be obtained if indicated. 
2 At the screening visit (optional) or on Day 1 prior to study vaccination, 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 PIMMCs. 
{}Targeted physical examination if indicated based on review of interim medical history. 
^ Performed locally by the site at the screening visit (optional) or within 24 hours prior to study vaccination for all women of childbearing potential. Results 
must be negative and known prior to randomization on Day 1 and administration of study vaccination. 
≠ Performed locally by the site at the screening visit (optional) or on Day 1 prior to study vaccination. The ESR value must be confirmed as less than 30 mm per 
hour prior to randomization on Day 1 and administration of study vaccination. 
~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr. 
# Clinical safety laboratory evaluations assessed on Day 1 prior to study vaccination will be considered as baseline. 
π Approximately 5 mL of each venous blood sample is designated for future research. 
? Specified sites will process blood for PBMCs isolation. Venous blood samples designated for future research will be drawn as indicated in the “Serological 
Assaysπ” row. 
Ψ Subjects who withdraw after receiving 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 study vaccination. These subjects will also be encouraged to provide a 
venous blood sample for serological assays approximately 21 and 180 days after their study vaccination, if feasible. 
& Inclusive of reactogenicity assessments performed on the day of each study vaccination through 7 days after study vaccination. 
3 AEs limited to SAEs and MAAEs, including NOCMCs and PIMMCs, that have occurred since the previous clinic visit or phone call. 
 
 


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108 
Table 15: Early Termination and Unscheduled Visits 
Study Visit 
Early Termination 
(if needed) 
Unscheduled 
(if needed) 
Study Procedure/Evaluation 
Interim Medical History 
X 
X (if indicated) 
Concomitant Medications 
X (if prior to 21 days 
study vaccination and 
receipt of any non-study 
influenza vaccines if 
within 180 days after 
study vaccination) 
X (if prior to 21 days 
after study vaccination 
and receipt of any non-
study influenza vaccines 
if within 180 days after 
study vaccination) 
Vital Signs (Oral Temperature%, Pulse and BP) 
X (may be obtained if 
indicated) 
X (may be obtained if 
indicated) 
Targeted Physical Examination 
X (if indicated) 
X (if indicated) 
Venous Blood Collection for Clinical Safety Laboratory Evaluations~ 
X (if within 7 days after 
study vaccination) 
X (if indicated) 
Venous Blood Collection for Serological Assaysπ 
X (if within 21 days 
after study vaccination) 
X (if within 21 days after 
study vaccination) 
Venous Blood Collection for Future Use? 
X (if within 21 days 
after study vaccination) 
X (if within 21 days after 
study vaccination) 
Examine Study Vaccination Site 
X (if within 7 days after 
study vaccination) 
X (if within 7 days after 
study vaccination) 
Post-Administration Reactogenicity Assessments 
X (if within 7 days after 
study vaccination) 
X (if within 7 days after 
study vaccination) 
Review Memory Aid 
X (if within 7 days after 
study vaccination) 
X (if within 7 days after 
study vaccination) 
AE/SAE Assessment3 
X (if after 21 days after 
study vaccination) 
X (if after 21 days after 
study vaccination) 
% Subjects must not eat or drink anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr. 
π Approximately 5 mL of each venous blood sample is designated for future research. 
? Specified sites will process blood for PBMCs isolation. Venous blood samples designated for future research will 
be drawn as indicated in the “Serological Assaysπ” row. 
3 AEs limited to SAEs and MAAEs, including NOCMCs and PIMMCs, that have occurred since the previous clinic 
visit or phone call. 
 


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109 
APPENDIX B. LIST OF POTENTIALLY IMMUNE-MEDIATED 
MEDICAL CONDITIONS (PIMMCS) 
(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 
• 
Systemic sclerosis 


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110 
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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111 
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 17-0090 
 
A Phase II Study to Assess the Safety, Reactogenicity and Immunogenicity of a 
Single Dose of 2017 A/H7N9 Inactivated Influenza Vaccine (IIV) Administered 
Intramuscularly with or without AS03 Adjuvant in 2013 A/H7N9 IIV Primed or 
A/H7 Naïve Subjects 
 
 
NCT03738241 
 
Version 1.0 
 
DATE: 14JAN2021 
 
THIS COMMUNICATION IS PRIVILEGED AND CONFIDENTIAL  
 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- ii - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
STUDY TITLE 
Protocol Number Code: 
DMID Protocol: 17-0090 
Development Phase: 
Phase II 
Products: 
Monovalent inactivated split influenza A/H7N9/Hong 
Kong/125/2017 virus vaccine (2017 A/H7N9 IIV) 
manufactured by Sanofi Pasteur (SP) 
AS03 adjuvant manufactured by GlaxoSmithKline 
Biologicals (GSK) 
Phosphate buffered saline (PBS) diluent manufactured by 
Patheon Manufacturing Services LLC 
 
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: 
December 12, 2018 
Clinical Trial Completion Date: 
June 19, 2020 
Date of the Analysis Plan: 
January 14, 2021 
Version Number: 
1.0 
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. 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
TABLE OF CONTENTS 
STUDY TITLE ............................................................................................................................... II 
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 
3.1.3. 
Exploratory ...................................................................................................................3 
3.2. 
Endpoints ......................................................................................................................3 
3.2.1. 
Primary .........................................................................................................................3 
3.2.2. 
Secondary .....................................................................................................................4 
3.2.3. 
Exploratory ...................................................................................................................4 
3.3. 
Study Definitions and Derived Variables .....................................................................5 
4. 
INVESTIGATIONAL PLAN .......................................................................................6 
4.1. 
Overall Study Design and Plan .....................................................................................6 
4.2. 
Discussion of Study Design, Including the Choice of Control Groups ........................6 
4.3. 
Selection of Study Population ......................................................................................6 
4.4. 
Treatments ....................................................................................................................7 
4.4.1. 
Treatments Administered ..............................................................................................7 
4.4.2. 
Identity of Investigational Product(s) ...........................................................................7 
4.4.3. 
Method of Assigning Subjects to Treatment Groups (Randomization) .......................7 
4.4.4. 
Selection of Doses in the Study ....................................................................................7 
4.4.5. 
Selection and Timing of Dose for Each Subject ...........................................................7 
4.4.6. 
Blinding ........................................................................................................................7 
4.4.7. 
Prior and Concomitant Therapy ....................................................................................7 
4.4.8. 
Treatment Compliance ..................................................................................................8 
4.5. 
Efficacy (Immunogenicity) and Safety Variables ........................................................8 
4.5.1. 
Safety Variables ............................................................................................................8 
4.5.2. 
Immunogenicity Variables ............................................................................................9 


Statistical Analysis Plan - DMID Protocol: 17-0090 
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5. 
SAMPLE SIZE CONSIDERATIONS .......................................................................10 
6. 
GENERAL STATISTICAL CONSIDERATIONS ....................................................11 
6.1. 
General Principles .......................................................................................................11 
6.2. 
Timing of Analyses .....................................................................................................11 
6.2.1. 
CSR .............................................................................................................................11 
6.3. 
Analysis Populations ..................................................................................................12 
6.3.1. 
Safety Population ........................................................................................................12 
6.3.2. 
Modified Intent-to-Treat (mITT) Population ..............................................................12 
6.3.3. 
Per Protocol Population ..............................................................................................12 
6.4. 
Covariates and Subgroups ..........................................................................................12 
6.5. 
Missing Data ...............................................................................................................12 
6.6. 
Interim Analyses and Data Monitoring ......................................................................13 
6.6.1. 
Interim Safety Review ................................................................................................13 
6.6.2. 
Interim Immunogenicity Review ................................................................................13 
6.7. 
Multicenter Studies .....................................................................................................13 
6.8. 
Multiple Comparisons/Multiplicity ............................................................................14 
7. 
STUDY SUBJECTS ...................................................................................................15 
7.1. 
Disposition of Subjects ...............................................................................................15 
7.2. 
Protocol Deviations ....................................................................................................15 
8. 
IMMUNOGENICITY EVALUATION .....................................................................16 
8.1. 
Primary Immunogenicity Analysis .............................................................................16 
8.2. 
Secondary Immunogenicity Analyses ........................................................................16 
8.3. 
Exploratory Immunogenicity Analyses ......................................................................16 
8.3.1. 
Covariate Analysis ......................................................................................................16 
8.3.2. 
Regression Modeling ..................................................................................................17 
8.3.3. 
Analysis of Heterologous Strains ...............................................................................17 
8.3.4. 
NA Serum Antibody Responses .................................................................................17 
9. 
SAFETY EVALUATION ..........................................................................................18 
9.1. 
Demographic and Other Baseline Characteristics ......................................................18 
9.1.1. 
Prior and Concurrent Medical Conditions ..................................................................18 
9.1.2. 
Prior and Concomitant Medications ...........................................................................18 
9.2. 
Measurements of Treatment Compliance ...................................................................18 
9.3. 
Adverse Events ...........................................................................................................19 


Statistical Analysis Plan - DMID Protocol: 17-0090 
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9.3.1. 
Solicited Events and Symptoms .................................................................................19 
9.3.2. 
Unsolicited Adverse Events ........................................................................................19 
9.4. 
Deaths, Serious Adverse Events and other Significant Adverse Events ....................20 
9.5. 
Pregnancies .................................................................................................................20 
9.6. 
Clinical Laboratory Evaluations .................................................................................21 
9.7. 
Vital Signs and Physical Evaluations .........................................................................21 
9.8. 
Concomitant Medications ...........................................................................................21 
10. 
REPORTING CONVENTIONS ................................................................................22 
11. 
TECHNICAL DETAILS ............................................................................................23 
12. 
SUMMARY OF CHANGES IN THE CONDUCT OF THE STUDY OR 
PLANNED ANALYSES ............................................................................................24 
13. 
REFERENCES ...........................................................................................................25 
14. 
APPENDICES ............................................................................................................26 
APPENDIX 1. TABLE MOCK-UPS..........................................................................................27 
APPENDIX 2. FIGURE MOCK-UPS ......................................................................................129 
APPENDIX 3. LISTINGS MOCK-UPS ...................................................................................146 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
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LIST OF ABBREVIATIONS 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
Bili 
Total Bilirubin 
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 
F 
Fahrenheit 
FDA 
U.S. Food and Drug Administration 
GMT 
Geometric Mean Titer 
HA 
Hemagglutinin 
HAI 
 
Hemagglutination Inhibition Antibody 
Hgb 
Hemoglobin 
ICH 
International Conference on Harmonisation 
IIV 
Inactivated Influenza Vaccine 
IM 
Intramuscularly 
IRB 
Institutional Review Board 
mcg 
Microgram 
MedDRA 
Medical Dictionary for Regulatory Activities  
mg 
Milligram 
mITT 
Modified Intent to Treat 
mL 
Milliliter 
N, n 
Number (typically refers to subjects) 
NA 
Neuraminidase 
Neut 
Neutralizing Antibody 
NIH 
National Institutes of Health 


Statistical Analysis Plan - DMID Protocol: 17-0090 
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NOCMC 
New Onset Chronic Medical Condition 
PI 
Principal Investigator 
PIMMC 
Potential Immune Mediated Medical Condition 
PLT 
Platelets 
PP 
Per Protocol 
PT 
Preferred Term 
RCD 
Reverse Cumulative Distribution  
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SDCC 
Statistical and Data Coordinating Center 
SMC 
Safety Monitoring Committee 
SOC  
System Organ Class 
SOP 
Standard Operating Procedures 
TFLs 
Tables, Figures, and Listings 
WBC 
White Blood Cell 
WHO 
World Health Organization 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
1. 
PREFACE 
This Statistical Analysis Plan (SAP) for DMID Protocol 17-0090, “A Phase II Study to Assess the Safety, 
Reactogenicity and Immunogenicity of a Single Dose of 2017 A/H7N9 Inactivated Influenza Vaccine (IIV) 
Administered Intramuscularly with or without AS03 Adjuvant in 2013 A/H7N9 IIV Primed or A/H7 Naïve 
Subjects,” 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, and listings (TFLs) planned for final 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 this SAP provides sufficient detail to meet the requirements 
identified by the U.S. Food and Drug Administration (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 with varying degrees of exposure to the 2013 
A/H7N9 IIV, the safety, reactogenicity, and immunogenicity of one dose of a monovalent inactivated 
influenza A/H7N9 virus vaccine administered IM with or without AS03 adjuvant. Subjects may have been 
vaccinated with the 2013 A/H7N9 IIV with or without AS03 or MF59 adjuvant or may be A/H7 naïve. 
2.1. 
Purpose of the Analyses 
These analyses will assess the safety and immunogenicity of a single dose of 2017 A/H7N9 IIV administered 
IM with or without AS03 adjuvant in 2013 A/H7N9 IIV primed or A/H7 IIV naïve subjects and will be 
included in the CSR. 


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3. 
STUDY OBJECTIVES AND ENDPOINTS 
3.1. 
Study Objectives 
3.1.1. 
Primary 
Safety: 
• To assess the safety and reactogenicity of 2017 A/H7N9 IIV given with or without AS03 adjuvant 
following receipt of one dose of study vaccine. 
Immunogenicity: 
• To assess the serum hemagglutination inhibition (HAI) and neutralizing (Neut) antibody responses 
following receipt of the study vaccine. 
3.1.2. 
Secondary 
Safety: 
• To assess unsolicited non-serious adverse events (AEs) following receipt of the study vaccine. 
• To assess medically attended adverse events (MAAEs), including new-onset chronic medical 
conditions (NOCMCs) and potentially immune-mediated medical conditions (PIMMCs), 
following receipt of the study vaccine. 
Immunogenicity: 
• To assess the kinetics and durability of serum HAI and Neut antibody responses following receipt 
of the study vaccine. 
3.1.3. 
Exploratory 
Immunogenicity: 
• To assess the effects of age, sex, body mass index (BMI), and prior receipt of seasonal or non-
study pandemic influenza vaccine(s) on serum HAI and Neut antibody responses following receipt 
of the study vaccine. 
• To determine, in at least a subset of samples, the serum antibody responses to N9 neuraminidase 
(NA). 
• To assess, in at least a subset of samples, hemaggluttinin (HA) stem-specific antibody responses. 
• 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. 
3.2. 
Endpoints 
3.2.1. 
Primary 
Safety 
• Occurrence of all serious adverse events (SAEs) from the time of study vaccination through 
approximately 12 months after study vaccination. 


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• Occurrence of solicited injection site and systemic reactogenicity events from the time of study 
vaccination through 7 days after study vaccination. 
• Occurrence of clinical safety laboratory AEs from the time of study vaccination through 
approximately 7 days after study vaccination. 
Immunogenicity: 
• For HAI and Neut antibodies, percentage of subjects achieving seroconversion against the 2017 
influenza A/H7N9 study vaccine virus (defined as either a pre-vaccination titer <10 and a post-
vaccination titer ≥40 or a pre-vaccination titer ≥10 and a minimum four-fold rise in post-
vaccination antibody titer) approximately 21 days after study vaccination. 
• For HAI and Neut antibodies, percentage of subjects achieving titer ≥40 against the 2017 influenza 
A/H7N9 study vaccine virus approximately 21 days after study vaccination. 
• Geometric mean titers (GMTs) of serum HAI and Neut antibodies against the 2017 influenza 
A/H7N9 study vaccine virus approximately 21 days after study vaccination. 
3.2.2. 
Secondary 
Safety: 
• Occurrence of all unsolicited non-serious AEs from the time of study vaccination through 
approximately 21 days after study vaccination. 
• Occurrence of all MAAEs, including NOCMCs and PIMMCs from the time of study vaccination 
through approximately 12 months after study vaccination. 
Immunogenicity: 
• For HAI and Neut antibodies, percentage of subjects seroconverting against the 2017 influenza 
A/H7N9 study vaccine virus approximately 7 and 180 days after study vaccination. 
• For HAI and Neut antibodies, percentage of subjects achieving a titer ≥40 against the 2017 
influenza A/H7N9 study vaccine virus approximately 7 and 180 days after study vaccination. 
• GMTs of serum HAI and Neut antibodies against the 2017 influenza A/H7N9 study vaccine virus 
approximately 7 and 180 days after study vaccination. 
• The percentage of subjects seroconverting, the percentage of subjects achieving a titer ≥40, and the 
GMTs of serum HAI and Neut antibodies against the 2013 influenza A/H7N9 vaccine virus 
(priming vaccine virus) approximately 21 days after study vaccination. 
3.2.3. 
Exploratory 
Immunogenicity: 
• For HAI and Neut antibodies, GMTs and percentage of subjects seroconverting against the 2017 
influenza A/H7N9 study vaccine virus approximately 21 days after study vaccination by age, sex, 
BMI, the inclusion of an adjuvant in the prime and/or boost regimens, and prior receipt of seasonal 
or non-study pandemic influenza vaccine(s). 
• GMTs and percentage of subjects seroconverting (defined as four-fold change from baseline) of 
serum anti-NA (by enzyme-linked immunosorbent assay [ELISA]) or anti-neuraminidase 


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inhibition (NAI) (by enzyme-linked lectin assay [ELLA]) antibodies immediately prior to and 7, 
21, and 180 days after study vaccination. 
• Correlation between the inclusion of an adjuvant in the prime and/or boost regimens with the 
elicited H7 HA and N9 NA-specific serum antibody titers approximately 21 days after study 
vaccination. 
• GMTs of HA stem-specific antibody immediately prior to and approximately 7, 21, and 180 days 
after study vaccination. 
• For HAI and Neut antibodies, GMTs and percentage of subjects seroconverting against 
antigenically drifted variants of influenza A/H7 viruses approximately 21 days after study 
vaccination. 
3.3. 
Study Definitions and Derived Variables  
Individual subject titers are calculated by taking the geometric mean of two replicate results at each time 
point. 
For individual subjects, fold rise will be calculated as the ratio of: 
𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝−𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡
𝑝𝑝𝑝𝑝𝑝𝑝−𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡 where pre-vaccination 
value is always the result obtained at Day 1, prior to the priming vaccination. 
Seroconversion for HAI and Neut assays is defined as either a pre-vaccination titer <10 and a post-vaccination 
titer ≥40, or a pre-vaccination titer ≥10 and a minimum four-fold rise in post-vaccination titer [5]. 


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4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design and Plan 
This is a Phase II clinical trial in up to 420 males and non-pregnant females, 19 to 70 years of age, inclusive, 
who are in good health and meet all eligibility criteria, which include a screening erythrocyte sedimentation 
rate (ESR) laboratory evaluation. This clinical trial is designed to assess the safety, reactogenicity and 
immunogenicity of one dose of a monovalent inactivated split influenza 2017 A/H7N9 virus vaccine (2017 
A/H7N9 IIV) manufactured by Sanofi Pasteur (SP), administered intramuscularly (IM) at 3.75 mcg 
hemagglutinin (HA) per dose, given with or without AS03 adjuvant manufactured by GlaxoSmithKline 
Biologicals (GSK), to subjects primed with a monovalent inactivated split influenza 2013 A/H7N9 virus 
vaccine (2013 A/H7N9IIV) in DMID Protocols 13-0032 and 13-0033, or to those who are A/H7 IIV-naïve. 
Phosphate buffered saline (PBS) diluent manufactured by Patheon Manufacturing Services LLC will be used 
to achieve the targeted dosage. 
Subjects who received the 2013 A/H7N9 IIV in DMID Protocols 13-0032 and 13-0033 or are A/H7 IIV-naïve 
will be stratified by prior receipt of 2013 A/H7N9 IIV, as well as by site and prior receipt of licensed, 
seasonal influenza vaccine (defined as receipt of at least one of the 2017-2018 and/or 2018-2019 licensed, 
seasonal influenza vaccines versus none), then randomly assigned in a 1:1 ratio to 1 of 2 treatment arms to 
receive 1 dose of 2017 A/H7N9 IIV at 3.75 mcg HA per dose with or without AS03 adjuvant (see Table 1). 
Reactogenicity will be measured by the occurrence of solicited injection site and systemic reactions from the 
time of study vaccination through 7 days after study vaccination. Unsolicited non-serious adverse events 
(AEs) will be collected from the time of study vaccination through approximately 21 days after study 
vaccination. SAEs, MAAEs, including NOCMCs and PIMMCs will be collected from the time of study 
vaccination through approximately 12 months after study vaccination. Clinical safety laboratory evaluations 
(hematology and chemistry) will be performed on venous blood collected immediately prior to study 
vaccination and approximately 7 days after study vaccination. 
Immunogenicity testing will include performing serological assays to assess hemagglutination inhibition 
(HAI), neutralizing (Neut), neuraminidase inhibition (NAI), neuraminidase (NA)-specific, and HA stem-
specific antibody titers at multiple time points following study vaccination. Venous blood will also be 
collected at multiple time points following study vaccination for the future research use of serum, plasma and 
peripheral blood mononuclear cells (PBMCs). 
Correlation of the H7 HA and N9 NA-specific serum antibody responses to the inclusion of an adjuvant in the 
prime and/or boost regimens will also be determined. 
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) at the same dose administered with or without AS03 adjuvant.  
4.3. 
Selection of Study Population 
This study was designed to enroll up to 420 2013 A/H7N9 IIV-primed – administered with or without AS03 
or MF59 - and A/H7 naïve males and non-pregnant females, 19 to 70 years of age, inclusive. 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.  


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4.4. 
Treatments 
4.4.1. 
Treatments Administered  
Influenza A/H7N9 vaccine, AS03 adjuvant, and PBS diluent will be administered. 
4.4.2. 
Identity of Investigational Product(s) 
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 prior receipt of 2013 A/H7N9 IIV with or without adjuvants, clinical 
site, and prior receipt of licensed, seasonal influenza vaccine then randomly assigned with allocation (1:1) to 
one of two treatment arms to receive 1 dose of 2017 A/H7N9 IIV at 3.75 mcg HA per dose with or without 
AS03 adjuvant. There is a total of ten strata with maximum enrollments outlined in Table 1. 
4.4.4. 
Selection of Doses in the Study 
Participants in this study are to receive one A/H7N9 vaccination at 3.75 mcg HA per dose with or without 
AS03 adjuvant. The 3.75 mcg dose is selected to evaluate the safety and immunogenicity of antigen sparing 
dose strategies after A/H7N9 prime. 
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 receipt of adjuvant for the 
study vaccination administered on Day 1. Study groups are defined by a combination of prior receipt of 2013 
A/H7N9 IIV and study product randomization as shown in Table 1. 
4.4.6. 
Blinding 
This trial is double-blinded; subjects, investigators, and study personnel performing any study-related 
assessments following study vaccine administration are blinded to adjuvant status. Laboratory personnel 
performing antibody assays are blinded to adjuvant status, subject ID, and visit number. 
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 would 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 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 
study vaccination or early termination (if prior to 21 days after study vaccination) will be solicited from the 


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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. 
In addition, receipt of any non-study influenza vaccines will be solicited through approximately 180 days after 
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. 
Prior receipt of a licensed seasonal influenza vaccine over the current (2018-2019) and previous season 
(2017-2018) is not exclusionary as long as it has been administered within the allowable window (protocol 
Section 5.1.2). 
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 are to receive a single dose of study product administered in the clinic. 
4.5. 
Efficacy (Immunogenicity) and Safety Variables 
See Table 2 and Table 3 for schedules of study procedures. 
4.5.1. 
Safety Variables 
Safety will be assessed by the frequency and severity: 
1. SAEs occurring from the time of study vaccination through approximately 12 months after study 
vaccination. 
2. Solicited AEs – reactogenicity events occurring from the time of study vaccination through 7 days 
after study vaccination: 
a. Injection site reactions including pruritus, ecchymosis, erythema, induration/edema, 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 study vaccination through approximately 7 
days after study vaccination. Parameters to be evaluated include white blood cell (WBC) count, 
hemoglobin (Hgb), platelets (PLT), alanine aminotransferase (ALT), total bilirubin (Bili), and 
creatinine (Cr). 
4. Vital sign AEs occurring from the time of study vaccination through approximately 7 days after study 
vaccination. Parameters to be evaluated include pulse, systolic and diastolic blood pressures, and oral 
temperature. 
5. Unsolicited AEs – non-serious AEs occurring from the time of study vaccination through 
approximately 21 days after study vaccination. 
6. MAAEs, including NOCMCs and PIMMCs, occurring from the time of study vaccination through 
approximately 12 months after study vaccination. 


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Grading scales for injection site and systemic solicited reactions, vital signs, and clinical laboratory 
parameters are provided in Table 9, Table 10, Table 11, and Table 12. 
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. 
NOCMCs are defined as any new ICD-10 diagnosis (10th revision of the International Statistical 
Classification of Diseases and Related Health Problems) that is applied to the subject during the course 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. 
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. For a list of 
PIMMCs currently if effect, refer to protocol Appendix B.  
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 10, values below the lower 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. 
An addendum to the SAP will be generated to outline the planned analyses for NA antigen specific antibody 
responses and HA stem-specific antibody responses when assay development is complete, and results are 
available. 
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 up to 420 subjects. The majority of subjects will be recruited from the 
population of subjects who received the 2013 A/H7N9 IIV in DMID Protocols 13-0032 and 13-0033. The 
sample size for this study was selected using estimates of recruitment based on the number of subjects 
completing these historical protocols and by 2013 A/H7N9 IIV vaccination history. Table 4 summarizes the 
vaccination history in these protocols and potential enrollment into this study. 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 5 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 treatment arms (N=30, 
50), in all subjects receiving adjuvant (N=210) or in the trial as a whole (N=420). 
Binomial confidence intervals (CIs) are widest (have the least precision) when the response rate is 50%. 
Table 6 is presented to indicate the worst-case scenario for precision of observed exact (Clopper-Pearson) 
binomial confidence intervals. 
Table 7 illustrates the minimum detectable differences in the proportion of subjects responding (e.g. attaining 
seroconversion or a titer ≥40) between any two treatment arms (N=30 or 50) using a two-sided Likelihood 
Ratio Test with alpha = 0.05. From previous experience with single dose studies, it is assumed that up to 3% 
of subjects will be excluded from the per protocol analysis with minimal effect on these calculations. 
Seroconversion rates of 10% to 90% are considered. 


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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 study group and subject, and when appropriate by visit number within subject. 
All summary tables will be structured with a column for each Study Group in the following order: 
• Group 1: 1 or 2 doses 2013 A/H7N9 + MF59 | 2017 A/H7N9 IIV 3.75mcg + AS03  
• Group 2: 1 or 2 doses 2013 A/H7N9 + MF59 | 2017 A/H7N9 IIV 3.75mcg 
• Group 3: 1 or 2 doses 2013 A/H7N9 + AS03 | 2017 A/H7N9 IIV 3.75mcg + AS03 
• Group 4: 1 or 2 doses 2013 A/H7N9 + AS03 | 2017 A/H7N9 IIV 3.75mcg 
• Group 5: 1 or 2 doses 2013 A/H7N9 15mcg or 45mcg | 2017 A/H7N9 IIV 3.75mcg + AS03 
• Group 6: 1 or 2 doses 2013 A/H7N9 15mcg or 45mcg | 2017 A/H7N9 IIV 3.75mcg 
• Group 7: 2013 A/H7N9 + MF59 or AS03 then 2013 A/H7N9 15mcg | 2017 A/H7N9 3.75mcg + 
AS03 
• Group 8: 2013 A/H7N9 + MF59 or AS03 then 2013 A/H7N9 15mcg | 2017 A/H7N9 3.75mcg 
• Group 9: A/H7N9 IIV-Naïve | 2017 A/H7N9 3.75mcg + AS03 
• Group 10: A/H7N9 IIV-Naïve | 2017 A/H7N9 3.75mcg 
All tables will be annotated with the total population size relevant to that table/arm, including any missing 
observations. 
6.2. 
Timing of Analyses 
6.2.1. 
CSR 
Once the last subject completes the visit that occurs approximately at Day 366, the clinical database will be 
cleaned, monitored, and locked. The CSR will be completed when all safety data through Day 366 and all 
humoral immunogenicity data through Day 180 are completed and uploaded. 
Upon receipt of humoral immunogenicity against influenza A/Hong Kong/125/2017 (H7N9), 
A/Shanghai/2/2013 (H7N9), and A/Guangdong/17SF003/2016 (H7N9) strains through Day 180 and 
subsequent non-clinical data lock, a subset of predefined “topline tables” will be generated by the SDCC 
concurrently with CSR generation. These tables will include summaries of safety and immunogenicity data 
and will represent the final analyses of primary and secondary endpoints; as such no p-value adjustment is 
required. These analyses may be made available to the sponsor for planning subsequent trials and to the lead 
PI for publication. Tables to be included in the topline set are indicated in this document 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. Additional exploratory immunogenicity endpoint data not available at the time of CSR 
preparation may be included in an addendum to the CSR 


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6.3. 
Analysis Populations 
6.3.1. 
Safety Population 
The safety population includes all subjects who received study vaccination. 
6.3.2. 
Modified Intent-to-Treat (mITT) Population 
The modified intent-to-treat (mITT) population includes all subjects who received study vaccination and 
contributed both pre- an at least one post-vaccination venous blood samples for immunogenicity testing (HAI 
and Neut antibody assays) for which valid results were reported. For analyses using the mITT population, any 
subject receiving a product that is different than the one they were randomized to receive will be examined 
and grouped on a case by case basis. 
6.3.3. 
Per Protocol Population 
The per-protocol (PP) population includes all subjects in the mITT population 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: 
o Receipt of non-study licensed, live vaccine within 30 days before or after study 
vaccination, 
o Receipt of non-study licensed, inactivated vaccine within 14 days before or after study 
vaccination, 
o Receipt of immunosuppressive therapy (e.g., corticosteroids) within 30 days before or 
after study vaccination. 
• Data from any visit that occurs more than one day out of window: 
o Visit 4 data collected before 5 days or after 10 days post vaccination; 
o Visit 6 data collected before 20 days or after 29 days post vaccination; 
o Visit 10 data collected before 166 days or after 195 days post vaccination. 
Analyses will be conducted using the PP population only if 10% or more of subjects are excluded from a 
primary or secondary analysis timepoint. For analyses using the PP population, subjects will be grouped based 
on study vaccination received. 
6.4. 
Covariates and Subgroups 
As a protocol defined exploratory analysis, HAI and Neut antibody response following vaccination will be 
summarized stratified by the following covariates: age (categorical: 19-35, 36-50, 51-70), sex (male, female), 
body mass index (<30, ≥30), and prior receipt of seasonal influenza vaccine(s) (receipt of 2017-2018 or 2018-
2019, or receipt of neither), 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 


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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. 
Clinical, safety, and reactogenicity data through approximately 365 days after study vaccination will represent 
the primary clinical database for this trial. Once the last subject completes the visit that occurs approximately 
365 days after study vaccination and all HAI and Neut results are received, a “topline” subset of the 
immunogenicity and safety tables will be provided to DMID on an expedited timeline.  These analyses may 
be made available to the sponsor for planning subsequent trials and to the lead PI for publication and 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 study 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 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 are no planned interim analyses for this study.  
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. 


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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. 
Disposition of Subjects 
Table 13 will present a summary of the reasons that subjects were screened but not enrolled. 
The disposition of subjects in the study will be tabulated by study group and stratum in Table 14. The table 
will show the total number of subjects screened, randomized, receiving the study vaccination, completing the 
blood draw for the primary immunogenicity endpoints, and completing the last visit. 
The number and percentage of enrolled subjects excluded from each analysis population by study group and 
stratum are presented in Table 15. A listing of subjects excluded from each analysis population will be 
presented in Listing 5. 
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 
study group and stratum in Figure 1. 
A listing of subjects who terminated early 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, study group, and stratum for all enrolled subjects in Table 8. Major deviations that will be reviewed for 
possible exclusion of immunogenicity results from the PP population include deviations related to 
eligibility/enrollment, 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 
Analysis of all immune responses will be conducted using the PP population. In addition, primary endpoint 
analyses will be conducted with the mITT population. Immune responses in terms of strain-specific A/H7N9 
HAI and Neut antibody titers will be summarized by study group 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 ≥40, percentage of subjects achieving seroconversion, and GMTs 
along with corresponding 95% CIs. Exact CIs will be presented for proportional endpoints. Summaries of 
primary and secondary immunogenicity endpoints are presented in Table 22, Table 23, Table 24, and 
Table 25. 
Reverse cumulative distribution (RCD) curves will be presented for HAI and Neut antibody titers against 
A/Hong Kong/125/2017 (H7N9), A/Shanghai/2/2013 (H7N9), and A/Guangdong/17SF003/2016 (H7N9) 
strains. Plots for each assay will be generated with 4 panels (pre-vaccination, 7 days post vaccination, 21 days 
post vaccination, and 180 days post vaccination) and separate curves within each panel for each study group 
and stratum, as shown in Figure 2, Figure 3, Figure 4, Figure 5, Figure 6, Figure 7, Figure 8, and Figure 9. 
HAI and Neut antibody GMTs against A/Hong Kong/125/2017 (H7N9), A/Shanghai/2/2013 (H7N9), and 
A/Guangdong/17SF003/2016 (H7N9) will be presented graphically with corresponding 95% CIs in Figure 10, 
Figure 11, Figure 12, Figure 13, Figure 14, Figure 15, Figure 16, and Figure 17. 
The spearman correlation between HAI and Neut antibody titers will be calculated at each time point over all 
stratum and group combinations for each strain. The correlation will be depicted in scatterplots as depicted in 
Figure 18, Figure 19, Figure 20, and Figure 21. 
Individual HAI and Neut assay results will be provided in Listing 9 and Listing 10, respectively. 
8.1. 
Primary Immunogenicity Analysis 
The primary immunogenicity endpoints of HAI and Neut seroconversion, percentage of subjects with titer 
≥40, and GMTs against the homologous A/H7N9 vaccine strain 21 days after study vaccination will be 
summarized as described above. Regression modeling of seroconversion and log titers is planned as described 
in Section 8.3.2. No formal hypothesis testing is planned. 
8.2. 
Secondary Immunogenicity Analyses 
The secondary immunogenicity endpoints of HAI and Neut seroconversion, percentage of subjects with titer 
≥40, and GMTs against the homologous A/H7N9 vaccine strain 7 and 180 days after study vaccination and 
the 2013 A/H7N9 vaccine strain 21 days after study vaccination will be summarized as described above. 
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 HAI and Neut antibodies against A/Hong 
Kong/125/2017 (H7N9) at 21 days post study vaccination will be summarized by study group, and stratified 
by prior receipt of 2013 A/H7N9 influenza vaccine in Table 26 and Table 27; by stratum and age (categorized 
as those subjects ages 19-35, 35-50, 51-70) in Table 28 and Table 29; by sex in Table 30 and Table 31; by 


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stratum and BMI in Table 32 and Table 33; and by stratum and prior receipt of seasonal influenza vaccines in 
Table 34 and Table 35. 
8.3.2. 
Regression Modeling 
Logistic and multivariable linear regression will be utilized to test for the effects of prior vaccination with 
2013 A/H7N9 IIV and the addition of AS03 adjuvant to 2017 A/H7N9 IIV on seroconversion and GMT at 21 
days post vaccination, respectively, for the PP population. Similar models will be fit for both HAI and Neut 
antibody results. 
Logistic regression will be fit to examine the relationship of HAI seroconversion at 21 days post vaccination 
with study group, stratum, and the interaction of study group and stratum. 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 post vaccination with study group, stratum, and the 
interaction of study group and stratum. Both models will be fit with and without adjustment for the following 
covariates (Z): sex (female, male), age (19-35 years, 35-50 years, 51-70 years), BMI (<30, ≥30), and prior 
receipt of seasonal influenza vaccine (none in past 2 seasons, at least one 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 36, Table 37, Table 38, and Table 39. Parameter estimates for the multiple linear 
regression models will be presented in Table 40, Table 41, Table 42, and Table 43. 
Model 1A: Logistic Regression (without covariate adjustment): 
𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙[𝑃𝑃(𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠)] = 𝛽𝛽0 + 𝛽𝛽1 × 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺+ 𝛽𝛽2 × 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 + 𝛽𝛽3 × 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺∗𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 
Model 1B: Logistic Regression (with covariate adjustment): 
𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙[𝑃𝑃(𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠)] = 𝛽𝛽0 + 𝛽𝛽1 × 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺+ 𝛽𝛽2 × 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆+ 𝛽𝛽3 × 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺∗𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆+ 𝛽𝛽4 × 𝑍𝑍 
Model 2A: Multiple Linear Regression (without covariate adjustment): 
𝑙𝑙𝑜𝑜𝑜𝑜(𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡) = 𝛽𝛽0 + 𝛽𝛽1 × 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺+ 𝛽𝛽2 × 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆+ 𝛽𝛽3 × 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺∗𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆+ 𝜀𝜀 
Model 2B: Multiple Linear Regression (with covariate adjustment): 
𝑙𝑙𝑙𝑙𝑙𝑙(𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡) = 𝛽𝛽0 + 𝛽𝛽1 × 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺+ 𝛽𝛽2 × 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆+ 𝛽𝛽3 × 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺∗𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆+ 𝛽𝛽4 × 𝑍𝑍+ 𝜀𝜀 
Subjects missing data for one or more covariates will be excluded from Models 1B and 2B. 
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. Results will be presented in Table 44 and Table 45 for A/Shanghai/2/2013 and in 
Table 46 and Table 47 for A/Guangdong/17F003/2016.A scatter plot of the correlation between response to 
the vaccine strain and each heterologous strain will be presented in Figure 23, Figure 24, Figure 25, and 
Figure 26. 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 population. Safety summaries will 
be presented overall and grouped by study group and 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 in Table 17 and Table 18 and by study group and stratum in Table 19 and Table 20. Age will be 
summarized as a continuous variable as well as by categories as defined in Section 8.3.1. Ethnicity is 
categorized as Hispanic or Latino, or not Hispanic or 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 
continuous as well as categorical, categorized as (<30, ≥30). Self-reported history of prior receipt of seasonal 
influenza vaccine will be categorized as follows: both 2017-2018 and 2018-2019, 2017-2018 only, 2018-2019 
only, receipt of none, or unknown. Demographic information for individual subjects will be provided in 
Listing 6. 
9.1.1. 
Prior and Concurrent 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 study group and stratum 
in Table 21. 
Individual subject listings will be presented for all reported medical history including prior and concurrent 
medical conditions in Listing 7. 
9.1.2. 
Prior and Concomitant 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, study group, and stratum for the safety population in Table 85. A listing of concomitant medications 
will be presented in Listing 18. 
9.2. 
Measurements of Treatment Compliance 
All subjects who were enrolled but not vaccinated will be presented by study group and stratum as part of the 
subject disposition in Table 14. Subjects receiving investigational product will be presented by site, stratum, 
and study group in Table 16. Listing 1 presents subjects who received investigational product with 
randomized study group, study product received, and stratum. 


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9.3. 
Adverse Events 
A summary of all adverse events is provided in Table 48. A summary of those events that occurred in ≥5% if 
subjects in any study group and stratum combination is provided in Table 49. 
9.3.1. 
Solicited Events and Symptoms 
Systemic solicited adverse events will be collected pre-vaccination and systemic and injection site solicited 
adverse events will be collected approximately 20 minutes post-vaccination and then daily for 7 days after 
study vaccination. Systemic events include fever, feverishness, fatigue, malaise, myalgia, arthralgia, headache 
and nausea and the grading scale for systemic events, including quantitative grading for fever is found in 
Table 10. Injection site events include injection site pruritus, injection site ecchymosis, injection site 
erythema, injection site induration/swelling, injection site pain and injection site tenderness. Ecchymosis, 
erythema and induration at the injection site are evaluated using both functional grade and measurement 
grading scales as defined in Table 9. 
When calculating the incidence of solicited events, each subject will be counted once at the highest severity 
and any repetitions will be ignored. When presenting solicited event summaries, the denominator for 
percentages will be the number of subjects who received the study 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 injection site symptom and any 
symptom. For each event, the denominator is the number of subjects who received the study vaccination with 
non-missing data for the specified event. The 95% CI calculated using Clopper-Pearson methodology from a 
binomial distribution (SAS Proc Freq with a binomial option) will be presented in Table 50. 
For each systemic event, each local event, any systemic event, any injection site event, and any solicited 
event, the maximum severity over 7 days after study vaccination will be summarized for the safety 
population. The number and percentage of subjects reporting each event will be summarized by the maximum 
severity, study group, and stratum. For each event the denominator is the number of subjects who received the 
study 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 in 
Table 51. 
The number of subjects reporting a solicited adverse event will be summarized for each day post vaccination 
as a summary in Table 52 and graphically in a bar chart in Figure 26 for systemic symptoms and Figure 27 for 
local symptoms. 
Systemic and injection site solicited events reported by subject will be presented in Listing 11 and Listing 12, 
sorted by subject ID, 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 for these summaries 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 in each stratum and study group 
will be summarized by MedDRA system organ class (SOC) and preferred term (PT). A 95% CI will be 


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presented for the percentage of subjects reporting any unsolicited event (serious or non-serious) for each 
MedDRA SOC and PT in Table 53. 
The following summaries for unsolicited AEs will be presented by MedDRA SOC, PT, study group, and 
stratum: 
• Incidence of AEs by severity and relationship to study product in Table 54; 
• Incidence of non-serious, related AEs by severity in Table 55; 
• Incidence of AEs over time (Days 1-8, Days 9-22 post study vaccination) in Table 56; 
• Incidence of non-serious, related AEs over time (Days 1-8, Days 9-22 post study vaccination) 
in Table 57 – note this table presents results for the secondary safety endpoint, “Occurrence of 
study vaccine-related unsolicited non-serious AEs from the time of study vaccination through 
approximately 21 days after study vaccination”; 
• Total frequency of AEs over time (Days 1-8, Days 9-22 post study vaccination) in Table 58; 
• Subject listing of non-serious AEs of moderate or great severity in Table 63; 
• Bar chart displaying total frequency of AEs by severity, MedDRA SOC, study group, and 
stratum in Figure 28; 
• Bar chart displaying incidence of AEs by severity, MedDRA SOC, study group, and stratum in 
Figure 29; 
• Bar charts displaying total frequency and incidence of AEs by relationship to study product, 
MedDRA SOC, study group, and stratum in Figure 30 and Figure 31, respectively; 
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, days post vaccination, reason reported as an SAE, relationship to study product, alternate etiology if not 
related, outcome, and duration of event in days: 
• Deaths and serious adverse events in Table 59; 
• Medically attended adverse events in Table 60; 
• New onset chronic medical conditions in Table 61; 
• Potentially immune mediated medical conditions in Table 62. 
A listing of all reported AEs by subject will be presented in Listing 13, sorted by stratum, study group, 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 19, Listing 20, Listing 21, Listing 22, 
and Listing 23 will present any study related pregnancies and their outcomes. 


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9.6. 
Clinical Laboratory Evaluations 
Clinical safety laboratory parameters (WBC, Hgb, PLT, ALT, Bili, Cr) will be collected from each subject 
prior to study vaccination and approximately 7 days after study vaccination. These evaluations will be 
performed by the central clinical laboratory. The grading scale for clinical laboratory evaluations is presented 
in Table 12. Clinical laboratory evaluations assessed on Day 1 prior to the study vaccination will be 
considered as baseline. 
The distribution of laboratory results by severity, study day, study group, and stratum will be presented in 
Table 66, Table 67, Table 68, Table 69, Table 73, Table 74, Table 75, and Table 76. Descriptive statistics 
including mean, standard deviation, median, maximum and minimum values by each study day will be 
summarized for each parameter and for the change from baseline for each parameter in Table 70, Table 71, 
Table 72, Table 73, Table 77, Table 78, Table 79, and Table 80. Box plots illustrating the change from 
baseline for each laboratory parameter will be presented in Figure 32, Figure 33, Figure 34, Figure 35, 
Figure 36, and Figure 37. Subject visits with abnormal laboratory results, mild severity or greater, will be 
presented in Table 64 and Table 65 for chemistry and hematology parameters, respectively. 
A complete listing of individual clinical laboratory results will be presented in Listing 14 and Listing 15 for 
chemistry and hematology, respectively, sorted by stratum, study group, subject ID, parameter, and visit. 
9.7. 
Vital Signs and Physical Evaluations 
Oral temperature, systolic blood pressure, diastolic blood pressure, and pulse will be assessed prior to study 
vaccination on Day 1 and these results will be considered as baseline. Additional measurements of vital signs 
may be taken on Day 2, Day 4, and Day 8 if indicated. The grading scale for vital sign evaluations is 
presented in Table 11. Summaries of vital signs by maximum severity will be tabulated for baseline and post-
baseline measurements, grouped by stratum and study group and presented in Table 80, Table 81, Table 82, 
Table 83, and Table 84. A listing of vital signs will be presented in Listing 16. 
Targeted physical examinations will be performed, if indicated, based on a subject’s medical history. A listing 
of physical exam findings will be presented in Listing 17. 
9.8. 
Concomitant Medications 
Concomitant medications will be collected for the 30 days prior to study vaccination through 21 days after 
study vaccination. Concomitant medications will be coded to the ATC using the WHO Drug Dictionary. The 
use of prior and concomitant medications taken during the study will be recorded on the eCRFs. A by-subject 
listing of concomitant medications during the study will be summarized by ATC1 code, ATC2 code, stratum, 
and study group for the safety population in Table 85. 


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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). 


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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 
topline report are indicated by *. 


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APPENDIX 1. TABLE MOCK-UPS 
 
 


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LIST OF TABLES 
Table 1: 
Study Design ...............................................................................................................33 
Table 2: 
Schedule of Study Procedures – Vaccination Period .................................................34 
Table 3: 
Schedule of Study Procedures – Early Termination and Unscheduled Visits ............37 
Table 4: 
Previously Primed Subjects for Potential Enrollment ................................................38 
Table 5: 
Power (%) to Detect Safety Events ............................................................................39 
Table 6: 
Precision of Binomial Confidence Intervals ...............................................................40 
Table 7: 
Minimum Detectable Difference in Proportion Responders ......................................41 
Table 8: 
Distribution of Protocol Deviations by Category, Type, and Stratum, All 
Enrolled Subjects ........................................................................................................42 
Table 9: 
Solicited Adverse Event Grading Scale – Injection Site ............................................46 
Table 10: Solicited Adverse Event Grading Scale – Systemic ...................................................47 
Table 11: Vital Signs Adverse Event Grading ............................................................................48 
Table 12: Laboratory Adverse Event Grading Scale ..................................................................49 
Table 13: Ineligibility Summary of Screen Failures ...................................................................50 
Table 14: Subject Disposition by Stratum and Study Group, All Enrolled Subjects .................51 
Table 15: Analysis Populations by Stratum and Study Group, All Enrolled Subjects ...............52 
Table 16: Dates of Vaccination by Site, Stratum and Study Group, Safety Population .............56 
Table 17: Summary of Categorical Demographic and Baseline Characteristics by Site, 
All Enrolled Subjects ..................................................................................................57 
Table 18: Summary of Continuous Demographic and Baseline Characteristics by Site ............59 
Table 19: Summary of Categorical Demographic and Baseline Characteristics by 
Stratum and Study Group, All Enrolled Subjects .......................................................60 
Table 20: Summary of Continuous Demographic and Baseline Characteristics by 
Stratum and Study Group, All Enrolled Subjects .......................................................62 
Table 21: Summary of Subjects with Pre-Existing Medical Conditions by MedDRA 
System Organ Class, Stratum and Study Group, Safety Population ..........................63 
Table 22: Summaries of Hemagglutination Inhibition Antibody Against A/Hong 
Kong/125/2017 (H7N9) by Study Day, Stratum and Study Group, Modified 
Intent-to-Treat Population* ........................................................................................64 
Table 23: Summaries of Hemagglutination Inhibition Antibody Against A/Hong 
Kong/125/2017 (H7N9) by Study Day, Stratum and Study Group, Per 
Protocol Population* ..................................................................................................65 


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Table 24: Summaries of Neutralizing Antibody Against A/Hong Kong/125/2017 
(H7N9) by Study Day, Stratum and Study Group, Modified Intent-to-Treat 
Population* .................................................................................................................65 
Table 25: Summaries of Neutralizing Antibody Against A/Hong Kong/125/2017 
(H7N9) by Study Day, Stratum and Study Group, Per Protocol Population* ............65 
Table 26: Summary of Hemagglutination Inhibition Antibody Against A/Hong 
Kong/125/2017 (H7N9) by Stratum and Study Group at 21 Days Post 
Vaccination, Per-Protocol Population* ......................................................................66 
Table 27: Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 
(H7N9) by Stratum and Study Group at 21 Days Post Vaccination, Per-
Protocol Population* ..................................................................................................67 
Table 28: Summary of Hemagglutination Inhibition Antibody Against A/Hong 
Kong/125/2017 (H7N9) by Stratum, Study Group and Age Group at 21 Days 
Post Vaccination, Per-Protocol Population .................................................................68 
Table 29: Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 
(H7N9) by Stratum, Study Group and Age Group at 21 Days Post 
Vaccination, Per-Protocol Population ........................................................................69 
Table 30: Summary of Hemagglutination Inhibition Antibody Against A/Hong 
Kong/125/2017 (H7N9) by Stratum, Study Group and Sex at 21 Days Post 
Vaccination, Per-Protocol Population ........................................................................70 
Table 31: Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 
(H7N9) by Study Group, Stratum, and Sex at 21 Days Post Vaccination, Per-
Protocol Population ....................................................................................................71 
Table 32: Summary of Hemagglutination Inhibition Antibody Against A/Hong 
Kong/125/2017 (H7N9) by Stratum, Study Group and BMI at 21 Days Post 
Vaccination, Per-Protocol Population* ......................................................................72 
Table 33: Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 
(H7N9) by Stratum, Study Group and BMI at 21 Days Post Vaccination, 
Per-Protocol Population* ............................................................................................73 
Table 34: Summary of Hemagglutination Inhibition Antibody Against A/Hong 
Kong/125/2017 (H7N9) by Stratum, Study Group and Prior Seasonal 
Influenza Vaccination at 21 Days Post Vaccination, Per-Protocol Population ..........74 
Table 35: Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 
(H7N9) by Stratum, Study Group and Prior Seasonal Influenza Vaccination 
at 21 Days Post Vaccination, Per-Protocol Population ..............................................75 
Table 36: Logistic Regression Model to Evaluate the Relationship of AS03 Adjuvant 
and Stratum with HAI Seroconversion Against A/Hong Kong/125/2017 
(H7N9) at 21 Days Post Study Vaccination, Per Protocol Population .......................76 


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Table 37: Logistic Regression Model to Evaluate the Relationship of AS03 Adjuvant 
and Stratum with Neut Seroconversion Against A/Hong Kong/125/2017 
(H7N9) at 21 Days Post Study Vaccination, Per Protocol Population .......................77 
Table 38: Logistic Regression Model to Evaluate the Relationship of AS03 Adjuvant 
and Stratum with HAI Seroconversion Against A/Hong Kong/125/2017 
(H7N9) at 21 Days Post Study Vaccination, Adjusted for Baseline 
Covariates, Per Protocol Population ...........................................................................78 
Table 39: Logistic Regression Model to Evaluate the Relationship of AS03 Adjuvant 
and Stratum with Neut Seroconversion Against A/Hong Kong/125/2017 
(H7N9) at 21 Days Post Study Vaccination, Adjusted for Baseline 
Covariates, Per Protocol Population ...........................................................................79 
Table 40: Multiple Linear Regression Model to Evaluate the Relationship of AS03 
Adjuvant and Stratum with Log-Adjusted HAI Titer Against A/Hong 
Kong/125/2017 (H7N9) at 21 Days Post Study Vaccination, Per Protocol 
Population ...................................................................................................................80 
Table 41: Multiple Linear Regression Model to Evaluate the Relationship of AS03 
Adjuvant and Stratum with Log-Adjusted Neut Titer Against A/Hong 
Kong/125/2017 (H7N9) at 21 Days Post Study Vaccination, Per Protocol 
Population ...................................................................................................................80 
Table 42: Multiple Linear Regression Model to Evaluate the Relationship of AS03 
Adjuvant and Stratum with Log-Adjusted HAI Titer Against A/Hong 
Kong/125/2017 (H7N9) at 21 Days Post Study Vaccination, Adjusted for 
Baseline Covariates, Per-Protocol Population ............................................................81 
Table 43: Multiple Linear Regression Model to Evaluate the Relationship of AS03 
Adjuvant and Stratum with Log-Adjusted Neut Titer Against A/Hong 
Kong/125/2017 (H7N9) at 21 Days Post Study Vaccination, Adjusted for 
Baseline Covariates, Per Protocol Population ............................................................82 
Table 44: Summaries of Hemagglutination Inhibition Antibody Against 
A/Shanghai/2/2013 (H7N9) by Study Day, Stratum and Study Group, Per-
Protocol Population ....................................................................................................83 
Table 45: Summaries of Neutralizing Antibody Against A/Shanghai/2/2013 (H7N9) by 
Study Day, Stratum and Study Group, Per Protocol Population ................................83 
Table 46: Summaries of Hemagglutination Inhibition Antibody Against 
A/Guangdong/17F003/2016 (H7N9) by Study Day, Stratum and Study 
Group, Per Protocol Population ..................................................................................84 
Table 47: Summaries of Neutralizing Antibody Against A/Guangdong/17F003/2016 
(H7N9) by Study Day, Stratum and Study Group, Per Protocol Population ..............84 
Table 48: Overall Summary of Adverse Events, Safety Population* .........................................85 
Table 49: Adverse Events Occurring in at least 5% of Subjects in Any Study Group by 
MedDRA System Organ Class and Preferred Term, Stratum and Study 
Group, Safety Population ............................................................................................88 


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Table 50: Number and Percentage of Subjects Experiencing Solicited Events with 95% 
Confidence Intervals by Symptom, Stratum and Study Group, Safety 
Population ...................................................................................................................92 
Table 51: Number and Percentage of Subjects Experiencing Solicited Events by 
Symptom, Maximum Severity, Stratum and Study Group, Safety Population ..........96 
Table 52: Number and Percentage of Subjects Experiencing Solicited Events by 
Symptom, Severity, Day Post Vaccination, Stratum and Study Group, Safety 
Population .................................................................................................................100 
Table 53: Number and Percentage of Subjects Experiencing Unsolicited Adverse 
Events with 95% Confidence Intervals by MedDRA System Organ Class 
and Preferred Term, Stratum and Study Group, Safety Population .........................104 
Table 54: Number and Percentage of Subjects Experiencing Unsolicited Adverse 
Events by MedDRA System Organ Class and Preferred Term, Maximum 
Severity, Relationship, Stratum and Study Group, Safety Population .....................106 
Table 55: Number and Percentage of Subjects Experiencing Non-Serious Related 
Unsolicited Adverse Events by MedDRA System Organ Class and Preferred 
Term, Maximum Severity, Stratum and Study Group, Safety Population ...............107 
Table 56: 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, Stratum and Study Group, 
Safety Population ......................................................................................................108 
Table 57: 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, Stratum and 
Study Group, Safety Population ...............................................................................109 
Table 58: Number of Unsolicited Adverse Events by MedDRA System Organ Class 
and Preferred Term, Day Post Vaccination, Stratum and Study Group, Safety 
Population .................................................................................................................110 
Table 59: Listing of Serious Adverse Events, Safety Population .............................................111 
Table 60: Listing of Medically Attended Adverse Events, Safety Population .........................112 
Table 61: Listing of New Onset Chronic Medical Conditions, Safety Population ...................112 
Table 62: Listing of Potentially Immune Mediated Medical Conditions, Safety 
Population .................................................................................................................112 
Table 63: Listing of Non-Serious, Unsolicited, Moderate or Severe Adverse Events, 
Safety Population ......................................................................................................112 
Table 64: Listing of Abnormal Laboratory Results – Chemistry, Safety Population ...............114 
Table 65: Listing of Abnormal Laboratory Results – Hematology, Safety Population............114 
Table 66: Laboratory Results by Parameter, Maximum Severity, Study Day, Stratum 
and Study Group – Any Chemistry Parameter, Safety Population ...........................116 


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Table 67: Laboratory Results by Parameter, Maximum Severity, Study Day, Stratum 
and Study Group - Alanine Aminotransferase, Safety Population ...........................117 
Table 68: Laboratory Results by Parameter, Maximum Severity, Study Day, Stratum 
and Study Group - Total Bilirubin, Safety Population .............................................117 
Table 69: Laboratory Results by Parameter, Maximum Severity, Study Day, Stratum 
and Study Group – Creatinine, Safety Population ....................................................117 
Table 70: Laboratory Summary Statistics by Parameter, Study Day, Stratum and Study 
Group – Alanine Aminotransferase (IU/L), Safety Population ................................118 
Table 71: Laboratory Summary Statistics by Parameter, Study Day, Stratum and Study 
Group – Total Bilirubin (mg/dL), Safety Population ...............................................118 
Table 72: Laboratory Summary Statistics by Parameter, Study Day, Stratum and Study 
Group – Creatinine, Safety Population .....................................................................118 
Table 73: Laboratory Results by Parameter, Maximum Severity, Study Day, Stratum 
and Study Group – Any Hematology Parameter, Safety Population........................119 
Table 74: Laboratory Results by Parameter, Maximum Severity, Study Day, Stratum 
and Study Group – Hemoglobin, Safety Population ................................................120 
Table 75: Laboratory Results by Parameter, Maximum Severity, Study Day, Stratum 
and Study Group – White Blood Cells (103/µL), Safety Population ........................121 
Table 76: Laboratory Results by Parameter, Maximum Severity, Study Day, Stratum 
and Study Group – Platelets (103/µL), Safety Population ........................................122 
Table 77: Laboratory Summary Statistics by Parameter, Study Day, Stratum and Study 
Group – Hemoglobin (g/dL), Safety Population ......................................................123 
Table 78: Laboratory Summary Statistics by Parameter, Study Day, Stratum and Study 
Group – White Blood Cells (103/µL), Safety Population .........................................123 
Table 79: Laboratory Summary Statistics by Parameter, Study Day, Stratum and Study 
Group – Platelets (103/µL), Safety Population .........................................................123 
Table 80: Vital Signs by Assessment, Maximum Severity, Study Day, Stratum and 
Study Group – Any Assessment, Safety Population ................................................124 
Table 81: Vital Signs by Assessment, Maximum Severity, Study Day, Stratum and 
Study Group - Oral Temperature, Safety Population ...............................................125 
Table 82: Vital Signs by Assessment, Maximum Severity, Study Day, Stratum and 
Study Group – Systolic Blood Pressure, Safety Population .....................................126 
Table 83: Vital Signs by Assessment, Maximum Severity, Study Day, Stratum and 
Study Group - Diastolic Blood Pressure, Safety Population ....................................127 
Table 84: Vital Signs by Assessment, Maximum Severity, Study Day, Stratum and 
Study Group - Pulse, Safety Population ...................................................................127 
Table 85: Number and Percentage of Subjects with Prior and Concurrent Medications 
by WHO Drug Classification, Stratum and Study Group, Safety Population ..........128 


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9.1 
Overall Study Design and Plan Description 
Table 1: 
Study Design 
2013 A/H7N9 Vaccination History 
Stratum 
Study Group / N 
Study Vaccination 
2013 A/H7N9 IIV + MF59  
1 / 50 
2017 A/H7N9 IIV 3.75 mcg + AS03 
2 / 50 
2017 A/H7N9 IIV 3.75 mcg 
2013 A/H7N9 IIV + AS03 
3 / 50 
2017 A/H7N9 IIV 3.75 mcg + AS03 
4 / 50 
2017 A/H7N9 IIV 3.75 mcg 
2013 A/H7N9 IIV 15 mcg or 45 mcg 
unadjuvanted  
5 / 50 
2017 A/H7N9 IIV 3.75 mcg + AS03 
6 / 50 
2017 A/H7N9 IIV 3.75 mcg 
2013 A/H7N9 IIV with MF59/AS03 then 
2013 A/H7N9 IIV 15 mcg  
7 / 30 
2017 A/H7N9 IIV 3.75 mcg + AS03 
8 / 30 
2017 A/H7N9 IIV 3.75 mcg 
A/H7 IIV-Naïve  
9 / 30 
2017 A/H7N9 IIV 3.75 mcg + AS03 
10 / 30 
2017 A/H7N9 IIV 3.75 mcg 
 


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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** 
V08+ 
V09** 
V10 
V11** 
Study Day post study vaccination 
Screening 
(Optional) 
D-28 to -1 
Enrollment 
Dose 
D1 
D2+1d 
D4+1d 
D8-1/+2d 
D15±1d 
D22+7d 
D61±7d 
D91±14d 
D121±14d 
D181±14d 
D366±14d 
Study Procedure/Evaluation 
Informed Consent∞ 
X 
X†¬ 
 
 
 
 
Demographic Information 
X 
X†* 
 
 
 
 
Eligibility Criteria 
X 
X†¬1 
 
 
 
 
 
 
 
 
 
 
Medical History@ 
X 
X†¬ 
X 
X 
X 
X 
X 
 
X 
X 
Concomitant Medicationsς 
X 
X†¬ 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs (Oral Temperature%, Pulse and BP) 
X 
X†$ 
X! 
X! 
X! 
 
 
 
Height and Weight 
X 
X†* 
 
 
 
 
Physical Examination 
X2 
{X†2*} 
{X} 
{X} 
{X} 
{X} 
{X} 
 
{X} 
{X} 
Urine or Serum Pregnancy Test 
X^ 
X†^ 
 
 
 
 
Venous Blood Collection for ESR 
X≠ 
X≠* 
 
 
 
 
Enrollment in AdvantageEDCSM and Randomization 
 
X† 
 
 
 
 
 
 
 
 
 
 
Venous Blood Collection for Clinical Safety Laboratory Evaluations~ 
X†# 
 
X 
 
 
 
Venous Blood Collection for Serological Assaysπ 
X† 
 
X 
 
XΨ 
 
XΨ 
Venous Blood Collection for Future Research? 
X† 
X 
X 
X 
X 
X 
 
X 
X 
Pre-Administration Reactogenicity Assessments 
X† 
 
 
 
 
Study Vaccination 
X 
 
 
 
 
20-minute Evaluation After Study Vaccination 
X 
 
 
 
 


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Study Visit Number 
V00 
V01 
V02+ 
V03+ 
V04 
V05+ 
V06 
V07** 
V08+ 
V09** 
V10 
V11** 
Study Day post study vaccination 
Screening 
(Optional) 
D-28 to -1 
Enrollment 
Dose 
D1 
D2+1d 
D4+1d 
D8-1/+2d 
D15±1d 
D22+7d 
D61±7d 
D91±14d 
D121±14d 
D181±14d 
D366±14d 
Study Procedure/Evaluation 
Examine Study Vaccination Site 
X 
X 
X 
X 
 
 
 
Post-Administration Reactogenicity Assessments 
X 
 
 
 
 
Distribute Memory Aid and Study-Related Materials 
X 
 
 
 
 
Review Memory Aid 
X 
X 
X 
 
 
 
AE/SAE Assessment 
X& 
X& 
X& 
X& 
X 
X 
X3 
X3 
X3 
X3 
X3 
+ 
May be performed as phone call assessment for sites not processing blood for PBMCs isolation. 
** 
Phone call assessment. 
∞ 
Prior to study procedures. 
¬ 
Review/confirm information or activity in subjects previously consented and screened. 
† 
Prior to study vaccination. 
* 
Not required if done at the optional screening visit. 
1 
Review results of ESR or clinical safety laboratory evaluations. 
@ 
Complete medical history will be obtained by interview of subjects at the screening visit (optional) or on Day 1 prior to study vaccination, and interim medical history will 
be obtained by interview of subjects at follow-up clinic visits after study vaccination. 
ς 
Concomitant medications limited to non-study influenza vaccines after Visit 06. 
% 
Subjects must not eat or drink anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
$ 
Vital signs assessed on Day 1 prior to study vaccination will be considered as baseline. 
! 
May be obtained if indicated. 
2 
At the screening visit (optional) or on Day 1 prior to study vaccination, 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 PIMMCs. 
{} 
Targeted physical examination if indicated based on review of interim medical history. 
^ 
Performed locally by the site at the screening visit (optional) or within 24 hours prior to study vaccination for all women of childbearing potential. Results must be negative 
and known prior to randomization on Day 1 and administration of study vaccination. 


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Study Visit Number 
V00 
V01 
V02+ 
V03+ 
V04 
V05+ 
V06 
V07** 
V08+ 
V09** 
V10 
V11** 
Study Day post study vaccination 
Screening 
(Optional) 
D-28 to -1 
Enrollment 
Dose 
D1 
D2+1d 
D4+1d 
D8-1/+2d 
D15±1d 
D22+7d 
D61±7d 
D91±14d 
D121±14d 
D181±14d 
D366±14d 
Study Procedure/Evaluation 
≠ 
Performed locally by the site at the screening visit (optional) or on Day 1 prior to study vaccination. The ESR value must be confirmed as less than 30 mm per hour prior to 
randomization on Day 1 and administration of study vaccination. 
~ 
Includes WBC, Hgb, PLT, ALT, T. Bili, Cr. 
# 
Clinical safety laboratory evaluations assessed on Day 1 prior to study vaccination will be considered as baseline. 
π 
Approximately 5 mL of each venous blood sample is designated for future research. 
? 
Specified sites will process blood for PBMCs isolation. Venous blood samples designated for future research will be drawn as indicated in the “Serological Assaysπ” row. 
Ψ 
Subjects who withdraw after receiving 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 study vaccination. These subjects will also be encouraged to provide a venous blood sample for serological 
assays approximately 21 and 180 days after their study vaccination, if feasible. 
& 
Inclusive of reactogenicity assessments performed on the day of each study vaccination through 7 days after study vaccination. 
3 
AEs limited to SAEs and MAAEs, including NOCMCs and PIMMCs, that have occurred since the previous clinic visit or phone call. 


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Table 3: 
Schedule of Study Procedures – Early Termination and Unscheduled Visits 
Study Visit 
Early Termination 
(if needed) 
Unscheduled 
(if needed) 
Study Procedure/Evaluation 
Interim Medical History 
X 
X (if indicated) 
Concomitant Medications 
X (if prior to 21 days 
study vaccination and 
receipt of any non-study 
influenza vaccines if 
within 180 days after 
study vaccination) 
X (if prior to 21 days after 
study vaccination and 
receipt of any non-study 
influenza vaccines if 
within 180 days after study 
vaccination) 
Vital Signs (Oral Temperature%, Pulse and BP) 
X (may be obtained if 
indicated) 
X (may be obtained if 
indicated) 
Targeted Physical Examination 
X (if indicated) 
X (if indicated) 
Venous Blood Collection for Clinical Safety Laboratory Evaluations~ 
X (if within 7 days after 
study vaccination) 
X (if indicated) 
Venous Blood Collection for Serological Assaysπ 
X (if within 21 days after 
study vaccination) 
X (if within 21 days after 
study vaccination) 
Venous Blood Collection for Future Use? 
X (if within 21 days after 
study vaccination) 
X (if within 21 days after 
study vaccination) 
Examine Study Vaccination Site 
X (if within 7 days after 
study vaccination) 
X (if within 7 days after 
study vaccination) 
Post-Administration Reactogenicity Assessments 
X (if within 7 days after 
study vaccination) 
X (if within 7 days after 
study vaccination) 
Review Memory Aid 
X (if within 7 days after 
study vaccination) 
X (if within 7 days after 
study vaccination) 
AE/SAE Assessment3 
X (if after 21 days after 
study vaccination) 
X (if after 21 days after 
study vaccination) 
% 
Subjects must not eat or drink anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
~ 
Includes WBC, Hgb, PLT, ALT, T. Bili, Cr. 
π 
Approximately 5 mL of each venous blood sample is designated for future research. 
? 
Specified sites will process blood for PBMCs isolation. Venous blood samples designated for future research will be 
drawn as indicated in the “Serological Assaysπ” row. 
3 
AEs limited to SAEs and MAAEs, including NOCMCs and PIMMCs, that have occurred since the previous clinic visit 
or phone call. 
 
 


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9.7.1 Sample Size 
Table 4: 
Previously Primed Subjects for Potential Enrollment 
17-0090 Study Strata 
Dose 1 
Dose 2 
Completed All 
Visits 
Able to recruit 
50% 
Completers 
Able to recruit 
25% 
Completers 
One or two doses 2013 
A/H7N9 IIV with MF59 
396 
387 
385 
192 
96 
One or two doses 2013 
A/H7N9 IIV with AS03 
291 
278 
279 
137 
70 
One or two doses 2013 
A/H7N9 IIV 15 mcg or 45 
mcg unadjuvanted 
396 
383 
383 
191 
95 
2013 A/H7N9 IIV + 
MF59 or AS03 (1st) then 
2013 A/H7N9 IIV 15 mcg 
(2nd) 
199 
190 
193 
96 
48 
 
 


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Table 5: 
Power (%) to Detect Safety Events 
Event Frequency 
N=30 
N=50 
N=210 
N=420 
≥10% 
Very Common 
95 
>99 
>99 
>99 
≥1% 
Common 
26 
39 
87 
98 
≥0.1% 
Uncommon 
2 
4 
18 
34 
≥0.01% 
Rare 
<1 
<1 
2 
4 


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Table 6: 
Precision of Binomial Confidence Intervals 
N 
95% CI 
30 
31-69 
50 
35-65 
210 
43-57 
420 
45-55 


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Table 7: 
Minimum Detectable Difference in Proportion Responders 
N per Treatment Arm 
Proportion Responders 
in Comparator Group 
A 
80% Power 
Minimal Detectable Difference 
Proportion 
Responders in 
Comparator 
Group B 
N=30 
0.10 
0.29 
0.39 
0.20 
0.34 
0.54 
0.30 
0.35 
0.65 
0.40 
0.35 
0.75 
0.50 
0.33 
0.83 
0.60 
0.30 
0.90 
0.70 
0.25 
0.95 
0.80 
0.19 
0.99 
0.90 
0.10 
>0.99 
N=50 
0.10 
0.22 
0.32 
0.20 
0.26 
0.46 
0.30 
0.27 
0.57 
0.40 
0.27 
0.67 
0.50 
0.27 
0.77 
0.60 
0.25 
0.85 
0.70 
0.22 
0.92 
0.80 
0.17 
0.96 
0.90 
0.10 
>0.99 


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10.2 
Protocol Deviations 
Table 8: 
Distribution of Protocol Deviations by Category, Type, and Stratum, All Enrolled Subjects 
Category 
Deviation 
Type 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(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. 
# 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  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Category 
Deviation 
Type 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(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. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
 
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 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood not 
collected 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Too few 
aliquots 
obtained 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Specimen 
result not 
obtained 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Category 
Deviation 
Type 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(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. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
 
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 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
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Category 
Deviation 
Type 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(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. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
 
Treatment 
unblinded 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes: N = Number of subjects enrolled in given stratum; N* = Number of subjects enrolled in given stratum and study group. 


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12.2.2 Displays of Adverse Events 
Table 9: 
Solicited Adverse Event Grading Scale – Injection Site 
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 if pain 
medication is used, it is Over 
the Counter (OTC) and used 
for less than 24 hours 
Subject is aware of pain; 
there is interference with 
daily activity or OTC pain 
medication is used for more 
than 24 hours 
Subject is aware of pain, and it 
prevents daily activity or pain 
requires prescription medication 
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)/Edema 
(Swelling)* 
Does not interfere with daily 
activity 
Interferes with daily activity 
Prevents daily activity 
Local (Injection Site) Reactogenicity Measurements 
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)/Edema 
(Swelling)* 
<20 mm 
20 mm – 50 mm 
>50 mm 
 
 


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Table 10: 
Solicited Adverse Event Grading Scale – Systemic 
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)a 
No interference with 
daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Arthralgia (Joint Pain)a 
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) 
Feverb – oralc 
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 
a Not at injection site. 
b A fever can be considered not related to the study product if an alternative etiology can be documented. Oral temperature 
assessed on Day 1 prior to study vaccination will be considered as baseline. 
c Subjects must not eat or drink anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
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Table 11: 
Vital Signs Adverse Event Grading 
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 
 


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12.4.1 Individual Laboratory Measurements and Abnormal Laboratory Values 
Table 12: 
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 13: 
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 
Note:  
aMore than one criterion may be marked per subject. 
bDenominator for percentages is the total number of screen failures. 
 
 


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Table 14: 
Subject Disposition by Stratum and Study Group, All Enrolled Subjects 
Subject 
Disposition 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
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 
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 
Immunogenicity Analysis of 
Primary Immunogenicity 
Outcomesb 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Completed Primary Follow-
upa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Completed Final Study Visit  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes: N = Number of subjects enrolled in the given stratum; N* = Number of subjects enrolled in the given stratum and study group. 
aRefer to Listing 2 for reasons subjects terminated early. 
bRefer to Listing 5 for reasons subjects are excluded from the per protocol population. 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
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Table 15: 
Analysis Populations by Stratum and Study Group, All Enrolled Subjects 
Analysis 
Populations 
Reason Subjects 
Excluded 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV 
with MF59/AS03 
then 2013 A/H7N9 
IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
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 Not 
Received 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Baseline Results 
Available 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Post-Vaccination 
Results Available 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Per-Protocol, Day 
8 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination Not 
Received 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Baseline Results 
Available 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Day 8 Result 
Reported by Lab 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lost to Follow-up Before 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Non-Study 
Vaccination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
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Analysis 
Populations 
Reason Subjects 
Excluded 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV 
with MF59/AS03 
then 2013 A/H7N9 
IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
 
Receipt of 
Immunosuppressive 
medication 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 8 Visit Out of 
Window 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Per-Protocol, Day 
15 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination Not 
Received 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Baseline Results 
Available 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Day 15 Result 
Reported by Lab 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lost to Follow-up Before 
Day 15 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Non-Study 
Vaccination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of 
Immunosuppressive 
medication 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 15 Visit Out of 
Window 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Per-Protocol, Day 
22 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination Not 
Received 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 54 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Analysis 
Populations 
Reason Subjects 
Excluded 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV 
with MF59/AS03 
then 2013 A/H7N9 
IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
 
No Baseline Results 
Available 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Day 22 Result 
Reported by Lab 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lost to Follow-up Before 
Day 22 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Non-Study 
Vaccination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of 
Immunosuppressive 
medication 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 22 Visit Out of 
Window 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Per-Protocol, Day 
91 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination Not 
Received 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Baseline Results 
Available 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Day 91 Result 
Reported by Lab 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lost to Follow-up Before 
Day 91 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Non-Study 
Vaccination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 55 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Analysis 
Populations 
Reason Subjects 
Excluded 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV 
with MF59/AS03 
then 2013 A/H7N9 
IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
 
Receipt of 
Immunosuppressive 
medication 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 91 Visit Out of 
Window 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Per-Protocol, Day 
181 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination Not 
Received 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Baseline Results 
Available 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No Day 181 Result 
Reported by Lab 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lost to Follow-up Before 
Day 181 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Non-Study 
Vaccination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receipt of 
Immunosuppressive 
medication 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 181 Visit Out of 
Window 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes: N = Number of subjects enrolled in the given stratum; N* = Number of subjects enrolled in the given stratum and study group.  
 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 56 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 16: 
Dates of Vaccination by Site, Stratum and Study Group, Safety Population 
Dates of Dosing 
2013 A/H7N9 IIV + MF59  
(N=X) 
2013 A/H7N9 IIV + AS03 
(N=X) 
2013 A/H7N9 IIV 15 mcg or 
45 mcg unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
3.75 
mcg 
A/H7N9 
(N*=X) 
3.75 
mcg 
A/H7N9 
+ AS03 
(N*=X) 
All 
Subjects 
(N*=X) 
3.75 
mcg 
A/H7N9 
(N*=X) 
3.75 
mcg 
A/H7N9 
+ AS03 
(N*=X) 
All 
Subjects 
(N*=X) 
3.75 
mcg 
A/H7N9 
(N*=X) 
3.75 
mcg 
A/H7N9 
+ AS03 
(N*=X) 
All 
Subjects 
(N*=X) 
3.75 
mcg 
A/H7N9 
(N*=X) 
3.75 
mcg 
A/H7N9 
+ AS03 
(N*=X) 
All 
Subjects 
(N*=X) 
3.75 
mcg 
A/H7N9 
(N*=X) 
3.75 
mcg 
A/H7N9 
+ AS03 
(N*=X) 
All 
Subjects 
(N*=X) 
3.75 
mcg 
A/H7N9 
(N*=X) 
3.75 
mcg 
A/H7N9 
+ AS03 
(N*=X) 
All 
Subjects 
(N*=X) 
[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] 
Notes: N = Number of subjects in the safety population in the given stratum; N* = Number of subjects in the safety population in the given stratum and study group. 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 57 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.1.2 Demographic Data by Study Group 
Table 17: 
Summary of Categorical Demographic and Baseline Characteristics by Site, All Enrolled Subjects 
Variable 
Characteristic 
Baylor 
(N=X) 
Cincinnati 
Children’s  
(N=X) 
Emory 
(N=X) 
Kaiser 
Permanente 
(N=X) 
Emory 
Hope 
Clinic 
(N=X) 
University 
of Iowa 
(N=X) 
SLU 
(N=X) 
University 
of 
Maryland 
(N=X) 
UTMB 
(N=X) 
Vanderbilt  
(N=X) 
All 
Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Sex  
Male 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Female 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BMI 
< 30 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
≥ 30 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Age 
19-35 years 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
35-50 years 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
51-70 years 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ethnicity  
Not Hispanic or 
Latino 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
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 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Asian 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Native Hawaiian 
or Other Pacific 
Islander 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Black or African 
American 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 58 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Variable 
Characteristic 
Baylor 
(N=X) 
Cincinnati 
Children’s  
(N=X) 
Emory 
(N=X) 
Kaiser 
Permanente 
(N=X) 
Emory 
Hope 
Clinic 
(N=X) 
University 
of Iowa 
(N=X) 
SLU 
(N=X) 
University 
of 
Maryland 
(N=X) 
UTMB 
(N=X) 
Vanderbilt  
(N=X) 
All 
Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
 
White 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Multi-Racial 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior 
Seasonal 
Influenza 
Vaccination 
2017-2018 and 
2018-2019 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
2017-2018 only 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2018-2019 only 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Neither 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N = Number of subjects enrolled at the given site. 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 59 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 18: 
Summary of Continuous Demographic and Baseline Characteristics by Site 
 
Variable 
Statistic 
Baylor 
(N=X) 
Cincinnati 
Children’s  
(N=X) 
Emory 
(N=X) 
Kaiser 
Permanente 
(N=X) 
Emory 
Hope 
Clinic 
(N=X) 
University 
of Iowa 
(N=X) 
SLU 
(N=X) 
University 
of 
Maryland 
(N=X) 
UTMB 
(N=X) 
Vanderbilt  
(N=X) 
All 
Subjects 
(N=X) 
Age 
Mean 
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 
 
Median 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Maximum 
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 
 
Standard Deviation 
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 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Maximum 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Note: N = Number of subjects enrolled at the given site. 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 60 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 19: 
Summary of Categorical Demographic and Baseline Characteristics by Stratum and Study Group, All Enrolled Subjects 
Variable 
Characteristic 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 mcg 
or 45 mcg unadjuvanted 
(N=X) 
2013 A/H7N9 IIV 
with MF59/AS03 
then 2013 A/H7N9 
IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X)  
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 
mcg 
A/H7N9 
+ AS03 
(N*=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Sex  
Male 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Female 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 BMI 
< 30 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
≥ 30 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Age 
19-35 years 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
35-50 years 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
51-70 years 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ethnicity  
Not Hispanic or 
Latino 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
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 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Asian 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Native 
Hawaiian or 
Other Pacific 
Islander 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 61 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Variable 
Characteristic 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 mcg 
or 45 mcg unadjuvanted 
(N=X) 
2013 A/H7N9 IIV 
with MF59/AS03 
then 2013 A/H7N9 
IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X)  
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 
mcg 
A/H7N9 
+ AS03 
(N*=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
 
Black or 
African 
American 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
White 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Multi-Racial 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior Seasonal 
Influenza 
Vaccination 
2017-2018 and 
2018-2019 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
2017-2018 only 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2018-2019 only 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Neither 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes: N = Number of subjects enrolled in the given stratum; N* = Number of subjects enrolled in the given stratum and study group. 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 62 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 20: 
Summary of Continuous Demographic and Baseline Characteristics by Stratum and Study Group, All Enrolled Subjects 
 
 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV 
with MF59/AS03 
then 2013 A/H7N9 
IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
Variable 
Statistic 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X)  
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
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 
Notes: N = Number of subjects enrolled in the given stratum; N* = Number of subjects enrolled in the given stratum and study group. 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 63 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.1.3 Prior and Concurrent Medical Conditions 
Table 21: 
Summary of Subjects with Pre-Existing Medical Conditions by MedDRA System Organ Class, Stratum and Study Group, Safety 
Population 
MedDRA System Organ Class 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X)  
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
+ AS03 
(N*=X) 
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 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Notes: N = Number of subjects in the safety population in the given stratum; N* = Number of subjects in the safety population in the given stratum and study group; n = number of subjects reporting 
medical history within the specified SOC.  
A subject is only counted once per SOC. 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 64 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.2 
Immunogenicity Data 
14.2.1 Immune Response Against 2017 A/H7N9 
Table 22: 
Summaries of Hemagglutination Inhibition Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Day, Stratum and Study 
Group, Modified Intent-to-Treat Population* 
Time Point 
2013 A/H7N9 IIV + MF59  
(N=X) 
2013 A/H7N9 IIV + AS03 
(N=X) 
2013 A/H7N9 IIV 15 mcg or 
45 mcg unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
 (N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03   
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03   
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
Day 1 (Pre-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) 
7 Days Post 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) 
21 Days Post 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) 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 65 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Time Point 
2013 A/H7N9 IIV + MF59  
(N=X) 
2013 A/H7N9 IIV + AS03 
(N=X) 
2013 A/H7N9 IIV 15 mcg or 
45 mcg unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
 (N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03   
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03   
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(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) 
xxx.x 
(xxx.x,xxx.x) 
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 
 
 
 
 
 
 
 
 
 
 
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) 
Note: N = Number of subjects in the modified intent-to-treat population in the given stratum; N* = Number of subjects in the modified intent-to-treat population in the given stratum and study group; 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 23: 
Summaries of Hemagglutination Inhibition Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Day, Stratum and Study 
Group, Per Protocol Population* 
Table 24: 
Summaries of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Day, Stratum and Study Group, Modified 
Intent-to-Treat Population* 
Table 25: 
Summaries of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Day, Stratum and Study Group, Per 
Protocol Population* 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 26: 
Summary of Hemagglutination Inhibition Antibody Against A/Hong Kong/125/2017 (H7N9) by Stratum and Study Group at 21 
Days Post Vaccination, Per-Protocol Population* 
Stratum 
3.75 mcg A/H7N9  
(N=X)  
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
 
All Subjects 
(N=X) 
2013 A/H7N9 IIV + MF59  
 
 
 
 n  
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) 
Titer ≥ 1:40 - % (95% CI)b 
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) 
Seroconversion - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
2013 A/H7N9 IIV + AS03  
 
 
 
 n  
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) 
Titer ≥ 1:40 - % (95% CI)b 
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) 
Seroconversion - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
2013 A/H7N9 IIV 15 mcg or 45 mcg unadjuvanted 
 
 
 
 
 n  
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) 
Titer ≥ 1:40 - % (95% CI)b 
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) 
2013 A/H7N9 IIV with MF59/AS03 then 2013 A/H7N9 IIV 15 mcg  
 
 
 
 n  
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) 
Titer ≥ 1:40 - % (95% CI)b 
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) 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 67 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Stratum 
3.75 mcg A/H7N9  
(N=X)  
3.75 mcg A/H7N9  
+ AS03 
(N=X) 
 
All Subjects 
(N=X) 
Seroconversion - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
A/H7 IIV-Naive 
 
 
 
 n  
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) 
Titer ≥ 1:40 - % (95% CI)b 
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) 
Seroconversion - % (95% CI)b 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Notes: N = Number of subjects in the Per Protocol Population in the given study group; N* = Number of subjects in the Per Protocol Population in the given stratum and study group; 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 27: 
Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by Stratum and Study Group at 21 Days Post 
Vaccination, Per-Protocol Population* 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 68 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 28: 
Summary of Hemagglutination Inhibition Antibody Against A/Hong Kong/125/2017 (H7N9) by Stratum, Study Group and Age 
Group at 21 Days Post Vaccination, Per-Protocol Population 
 
2013 A/H7N9 IIV + MF59  
(N=X) 
2013 A/H7N9 IIV + AS03 
(N=X) 
2013 A/H7N9 IIV 15 mcg or 
45 mcg unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03  
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
Age 19-35 years 
 
 
 
 
 
 
 
 
 
 
 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) 
Age 35-50 years 
 
 
 
 
 
 
 
 
 
 
 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) 
Age 51-70 years 
 
 
 
 
 
 
 
 
 
 
 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) 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 69 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
 
2013 A/H7N9 IIV + MF59  
(N=X) 
2013 A/H7N9 IIV + AS03 
(N=X) 
2013 A/H7N9 IIV 15 mcg or 
45 mcg unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03  
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 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) 
xxx.x 
(xxx.x,xxx.x) 
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) 
Notes: N = Number of subjects in the per-protocol population in the given stratum; N* = Number of subjects in the per-protocol population in the given stratum and study group; 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 29: 
Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by Stratum, Study Group and Age Group at 21 Days 
Post Vaccination, Per-Protocol Population 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 70 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 30: 
Summary of Hemagglutination Inhibition Antibody Against A/Hong Kong/125/2017 (H7N9) by Stratum, Study Group and Sex at 
21 Days Post Vaccination, Per-Protocol Population 
 
2013 A/H7N9 IIV + MF59  
(N=X) 
2013 A/H7N9 IIV + AS03 
(N=X) 
2013 A/H7N9 IIV 15 mcg or 
45 mcg unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03  
(N*=X) 
3.75 mcg 
A/H7N9  
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
 (N*=X) 
3.75 mcg 
A/H7N9  
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03  
(N*=X) 
3.75 mcg 
A/H7N9  
(N*=X) 
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) 
Notes: N = Number of subjects in the per-protocol population in the given stratum; N* = Number of subjects in the per-protocol population in the given stratum and study group;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: 17-0090 
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Tables with similar format: 
Table 31: 
Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Group, Stratum, and Sex at 21 Days Post 
Vaccination, Per-Protocol Population 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 32: 
Summary of Hemagglutination Inhibition Antibody Against A/Hong Kong/125/2017 (H7N9) by Stratum, Study Group and BMI 
at 21 Days Post Vaccination, Per-Protocol Population* 
 
2013 A/H7N9 IIV + MF59  
(N=X) 
2013 A/H7N9 IIV + AS03 
(N=X) 
2013 A/H7N9 IIV 15 mcg or 45 
mcg unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 A/H7N9 
IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03  
(N*=X) 
3.75 mcg 
A/H7N9  
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
 (N*=X) 
3.75 mcg 
A/H7N9  
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03  
(N*=X) 
3.75 mcg 
A/H7N9  
(N*=X) 
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) 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
 
2013 A/H7N9 IIV + MF59  
(N=X) 
2013 A/H7N9 IIV + AS03 
(N=X) 
2013 A/H7N9 IIV 15 mcg or 45 
mcg unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 A/H7N9 
IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03  
(N*=X) 
3.75 mcg 
A/H7N9  
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
 (N*=X) 
3.75 mcg 
A/H7N9  
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03  
(N*=X) 
3.75 mcg 
A/H7N9  
(N*=X) 
Notes: N = Number of subjects in the per-protocol population in the given stratum; N* = Number of subjects in the per-protocol population in the given stratum and study group;  ; n = number of 
subjects with available result; 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 33: 
Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by Stratum, Study Group and BMI at 21 Days Post 
Vaccination, Per-Protocol Population* 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 34: 
Summary of Hemagglutination Inhibition Antibody Against A/Hong Kong/125/2017 (H7N9) by Stratum, Study Group and Prior 
Seasonal Influenza Vaccination at 21 Days Post Vaccination, Per-Protocol Population 
 
2013 A/H7N9 IIV + MF59  
(N=X) 
2013 A/H7N9 IIV + AS03 
(N=X) 
2013 A/H7N9 IIV 15 mcg or 
45 mcg unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
Did Not Receive 2017-2018 
or 2018-2019 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 2017-2018 and/or 
2018-2019 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) 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
 
2013 A/H7N9 IIV + MF59  
(N=X) 
2013 A/H7N9 IIV + AS03 
(N=X) 
2013 A/H7N9 IIV 15 mcg or 
45 mcg unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
Note: N = Number of subjects in the per-protocol population in the given stratum; N* = Number of subjects in the per-protocol population in the given stratum and study group; n = number of subjects 
with available result; 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 35: 
Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by Stratum, Study Group and Prior Seasonal 
Influenza Vaccination at 21 Days Post Vaccination, Per-Protocol Population 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 36: 
Logistic Regression Model to Evaluate the Relationship of AS03 Adjuvant and Stratum with HAI Seroconversion Against A/Hong 
Kong/125/2017 (H7N9) at 21 Days Post Study Vaccination, Per Protocol Population 
Model Parameter 
Parameter Levels 
Parameter 
Estimate 
SE 
p-value 
Odds Ratio 
95%CI 
Intercept 
- 
xxx.x 
xxx.x 
x.xxx 
- 
- 
Study Group 
3.75 mcg A/H7N9 (reference) 
- 
- 
- 
- 
- 
 
3.75 mcg A/H7N9 + AS03 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Stratum 
A/H7 IIV-Naive (reference) 
- 
- 
- 
- 
- 
 
2013 A/H7N9 IIV 15 mcg or 45 mcg 
unadjuvanted  
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 
2013 A/H7N9 IIV with MF59/AS03 then 
2013 A/H7N9 IIV 15 mcg  
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 
2013 A/H7N9 IIV + MF59  
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 
2013 A/H7N9 IIV + AS03  
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Study Group * Stratum 
A/H7 IIV-Naïve * 3.75 mcg A/H7N9 + 
AS03 
- 
- 
- 
- 
- 
 
2013 A/H7N9 IIV 15 mcg or 45 mcg 
unadjuvanted * 3.75 mcg A/H7N9 + AS03 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 
2013 A/H7N9 IIV with MF59/AS03 then 
2013 A/H7N9 IIV 15 mcg * 3.75 mcg 
A/H7N9 + AS03 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 
2013 A/H7N9 IIV + MF59 * 3.75 mcg 
A/H7N9 + AS03 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 
2013 A/H7N9 IIV + AS03 * 3.75 mcg 
A/H7N9 + AS03 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Note: N = XX subjects with results available at 21 days post vaccination in the per protocol population. XX subjects missing covariate data were excluded from this analysis. 
P-values will be generated for study group, stratum, and the study group by stratum interaction using a likelihood-ratio test.  
The p-value for the study group term was 0.xxx; The p-value for the stratum term was 0.xxx; The p-value for the study group by stratum interaction term was 0.xxx.  
 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
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Tables with similar format: 
Table 37: 
Logistic Regression Model to Evaluate the Relationship of AS03 Adjuvant and Stratum with Neut Seroconversion Against 
A/Hong Kong/125/2017 (H7N9) at 21 Days Post Study Vaccination, Per Protocol Population 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 38: 
Logistic Regression Model to Evaluate the Relationship of AS03 Adjuvant and Stratum with HAI Seroconversion Against A/Hong 
Kong/125/2017 (H7N9) at 21 Days Post 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 
- 
- 
Study Group 
3.75 mcg A/H7N9 (reference) 
- 
- 
- 
- 
- 
 
3.75 mcg A/H7N9 + AS03 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Stratum 
A/H7 IIV-Naive (reference) 
- 
- 
- 
- 
- 
 
2013 A/H7N9 IIV 15 mcg or 45 mcg 
unadjuvanted  
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 
2013 A/H7N9 IIV with MF59/AS03 then 
2013 A/H7N9 IIV 15 mcg  
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 
2013 A/H7N9 IIV + MF59  
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 
2013 A/H7N9 IIV + AS03  
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Interaction: Study Group*Stratum 
A/H7 IIV-Naïve * 3.75 mcg A/H7N9 + 
AS03 
- 
- 
- 
- 
- 
 
2013 A/H7N9 IIV 15 mcg or 45 mcg 
unadjuvanted * 3.75 mcg A/H7N9 + AS03 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 
2013 A/H7N9 IIV with MF59/AS03 then 
2013 A/H7N9 IIV 15 mcg * 3.75 mcg 
A/H7N9 + AS03 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 
2013 A/H7N9 IIV + MF59 * 3.75 mcg 
A/H7N9 + AS03 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 
2013 A/H7N9 IIV + AS03 * 3.75 mcg 
A/H7N9 + AS03 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Age 
 19-35 years (reference) 
- 
- 
- 
- 
- 
 
 35-50 years 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 
 51-70 years 
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) 
- 
- 
- 
- 
- 


Statistical Analysis Plan - DMID Protocol: 17-0090 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Model Parameter 
Parameter Levels 
Parameter 
Estimate 
SE 
p-value 
Odds Ratio 
95%CI 
 
 ≥30 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Prior Receipt of Influenza Vaccine 
 Did Not Receive 2017-2018 or 2018-2019 
Seasonal Influenza Vaccine (reference) 
- 
- 
- 
- 
- 
 
 Received 2017-2018 or 2018-2019 Seasonal 
Influenza Vaccine 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Note: N = XX subjects with results available at 21 days post vaccination in the per protocol population. XX subjects missing covariate data were excluded from this analysis. 
Tables with similar format: 
Table 39: 
Logistic Regression Model to Evaluate the Relationship of AS03 Adjuvant and Stratum with Neut Seroconversion Against 
A/Hong Kong/125/2017 (H7N9) at 21 Days Post Study Vaccination, Adjusted for Baseline Covariates, Per Protocol Population 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 40: 
Multiple Linear Regression Model to Evaluate the Relationship of AS03 Adjuvant and Stratum with Log-Adjusted HAI Titer 
Against A/Hong Kong/125/2017 (H7N9) at 21 Days Post Study Vaccination, Per Protocol Population 
Model Parameter 
Parameter Levels 
Parameter 
Estimate 
SE 
95% CI 
p-value 
Intercept 
- 
xxx.x 
xxx.x 
- 
x.xxx 
Study Group 
3.75 mcg A/H7N9 (reference) 
- 
- 
- 
- 
 
3.75 mcg A/H7N9 + AS03 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Stratum 
A/H7 IIV-Naive (reference) 
- 
- 
- 
- 
 
2013 A/H7N9 IIV 15 mcg or 45 mcg unadjuvanted  
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 
2013 A/H7N9 IIV with MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 
2013 A/H7N9 IIV + MF59  
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 
2013 A/H7N9 IIV + AS03  
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Interaction: Study Group*Stratum 
A/H7 IIV-Naïve * 3.75 mcg A/H7N9 + AS03 
- 
- 
- 
- 
 
2013 A/H7N9 IIV 15 mcg or 45 mcg unadjuvanted 
* 3.75 mcg A/H7N9 + AS03 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 
2013 A/H7N9 IIV with MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg * 3.75 mcg A/H7N9 + AS03 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 
2013 A/H7N9 IIV + MF59 * 3.75 mcg A/H7N9 + 
AS03 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 
2013 A/H7N9 IIV + AS03 * 3.75 mcg A/H7N9 + 
AS03 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Note: N = XX subjects with results available at 21 days post vaccination in the per-protocol population. XX subjects missing covariate data were excluded from this analysis. 
Tables with similar format: 
Table 41: 
Multiple Linear Regression Model to Evaluate the Relationship of AS03 Adjuvant and Stratum with Log-Adjusted Neut Titer 
Against A/Hong Kong/125/2017 (H7N9) at 21 Days Post Study Vaccination, Per Protocol Population 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 42: 
Multiple Linear Regression Model to Evaluate the Relationship of AS03 Adjuvant and Stratum with Log-Adjusted HAI Titer 
Against A/Hong Kong/125/2017 (H7N9) at 21 Days Post 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 A/H7N9 (reference) 
- 
- 
- 
- 
 
3.75 mcg A/H7N9 + AS03 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Stratum 
A/H7 IIV-Naive (reference) 
- 
- 
- 
- 
 
2013 A/H7N9 IIV 15 mcg or 45 mcg unadjuvanted  
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 
2013 A/H7N9 IIV with MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 
2013 A/H7N9 IIV + MF59  
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 
2013 A/H7N9 IIV + AS03  
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Interaction: Study Group*Stratum 
A/H7 IIV-Naïve * 3.75 mcg A/H7N9 + AS03 
- 
- 
- 
- 
 
2013 A/H7N9 IIV 15 mcg or 45 mcg unadjuvanted 
* 3.75 mcg A/H7N9 + AS03 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 
2013 A/H7N9 IIV with MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg * 3.75 mcg A/H7N9 + AS03 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 
2013 A/H7N9 IIV + MF59 * 3.75 mcg A/H7N9 + 
AS03 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 
2013 A/H7N9 IIV + AS03 * 3.75 mcg A/H7N9 + 
AS03 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Age 
 19-35 years (reference) 
- 
- 
- 
- 
 
 35-50 years 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 
 51-70 years 
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 


Statistical Analysis Plan - DMID Protocol: 17-0090 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Model Parameter 
Parameter Levels 
Parameter 
Estimate 
SE 
95% CI 
p-value 
Prior Receipt of Influenza Vaccine 
 Did Not Receive 2017-2018 or 2018-2019 
Seasonal Influenza Vaccine (reference) 
- 
- 
- 
- 
 
 Received 2017-2018 or 2018-2019 Seasonal 
Influenza Vaccine 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Note: N = XX subjects with results available at 21 days post vaccination in the per-protocol population. XX subjects missing covariate data were excluded from this analysis. 
Tables with similar format: 
Table 43: 
Multiple Linear Regression Model to Evaluate the Relationship of AS03 Adjuvant and Stratum with Log-Adjusted Neut Titer 
Against A/Hong Kong/125/2017 (H7N9) at 21 Days Post Study Vaccination, Adjusted for Baseline Covariates, Per Protocol 
Population 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 83 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 44: 
Summaries of Hemagglutination Inhibition Antibody Against A/Shanghai/2/2013 (H7N9) by Study Day, Stratum and Study 
Group, Per-Protocol Population 
Time Point 
2013 A/H7N9 IIV + MF59  
(N=X) 
2013 A/H7N9 IIV + AS03 
(N=X) 
2013 A/H7N9 IIV 15 mcg or 
45 mcg unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
Day 1 (Pre-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) 
21 Days Post 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) 
Notes: N = number of subjects in the per-protocol population in the given stratum; N* = Number of subjects in the per-protocol population in the given stratum and study group; n = number of subjects 
with available result; 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 45: 
Summaries of Neutralizing Antibody Against A/Shanghai/2/2013 (H7N9) by Study Day, Stratum and Study Group, Per Protocol 
Population 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 46: 
Summaries of Hemagglutination Inhibition Antibody Against A/Guangdong/17F003/2016 (H7N9) by Study Day, Stratum and 
Study Group, Per Protocol Population 
Time Point 
2013 A/H7N9 IIV + MF59  
(N=X) 
2013 A/H7N9 IIV + AS03 
(N=X) 
2013 A/H7N9 IIV 15 mcg or 
45 mcg unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
3.75 mcg 
A/H7N9 
(N*=X) 
3.75 mcg 
A/H7N9 + 
AS03 
(N*=X) 
Day 1 (Pre-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) 
21 Days Post 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) 
Notes: N = Number of subjects in the per-protocol population in the given stratum; N* = Number of subjects in the per-protocol population in the given stratum and study group; 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 47: 
Summaries of Neutralizing Antibody Against A/Guangdong/17F003/2016 (H7N9) by Study Day, Stratum and Study Group, Per 
Protocol Population 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
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14JAN2021 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.3 
Safety Data 
14.3.1 Displays of Adverse Events 
Table 48: 
Overall Summary of Adverse Events, Safety Population* 
 
2013 A/H7N9 
IIV + MF59  
(N=X) 
2013 A/H7N9 
IIV + AS03 
(N=X) 
2013 A/H7N9 
IIV 15 mcg or 45 
mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 
IIV with 
MF59/AS03 then 
2013 A/H7N9 
IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects  
(N=X) 
3.75 mcg A/H7N9 IIV (N*=X) 
Subjectsa with 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
At least one injection site 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 
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 
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 
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 
At least one clinical safety laboratory 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 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
 
2013 A/H7N9 
IIV + MF59  
(N=X) 
2013 A/H7N9 
IIV + AS03 
(N=X) 
2013 A/H7N9 
IIV 15 mcg or 45 
mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 
IIV with 
MF59/AS03 then 
2013 A/H7N9 
IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects  
(N=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 
3.75 mcg A/H7N9 IIV + AS03 (N*=X) 
Subjectsa with 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
At least one injection site 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 
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 
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 
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 
At least one clinical safety laboratory 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 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 87 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
 
2013 A/H7N9 
IIV + MF59  
(N=X) 
2013 A/H7N9 
IIV + AS03 
(N=X) 
2013 A/H7N9 
IIV 15 mcg or 45 
mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 
IIV with 
MF59/AS03 then 
2013 A/H7N9 
IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects  
(N=X) 
     Severe (Grade 3) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
At least one vital signs 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 
Notes: N = Number of subjects in the safety population who received study vaccination in the given stratum; N* = Number of subjects in the safety population in the given study group; n = number of 
subjects with available results. 
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 59 
c As reported on the Adverse Event eCRF 


Statistical Analysis Plan - DMID Protocol: 17-0090 
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14JAN2021 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 49: 
Adverse Events Occurring in at least 5% of Subjects in Any Study Group by MedDRA System Organ Class and Preferred Term, 
Stratum and Study Group, Safety Population 
Preferred Term 
MedDRA System 
Organ Class 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 
15 mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV 
with MF59/AS03 
then 2013 
A/H7N9 IIV 15 
mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
 
 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
3.75 mcg A/H7N9 IIV (N*=X) 
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. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Solicited 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. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical Safety Laboratory 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. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital Signs 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 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 89 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Preferred Term 
MedDRA System 
Organ Class 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 
15 mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV 
with MF59/AS03 
then 2013 
A/H7N9 IIV 15 
mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
Etc. 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Total 
All  
All 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
3.75 mcg A/H7N9 IIV + AS03 (N*=X) 
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 
SOC1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Solicited 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. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical Safety Laboratory 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. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital Signs 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 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 90 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Preferred Term 
MedDRA System 
Organ Class 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 
15 mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV 
with MF59/AS03 
then 2013 
A/H7N9 IIV 15 
mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
Etc. 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Total 
All  
All 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
All Subjects (N*=X) 
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 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
SOC1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Solicited 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. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical Safety Laboratory 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. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Total 
All  
All 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 91 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Preferred Term 
MedDRA System 
Organ Class 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 
15 mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV 
with MF59/AS03 
then 2013 
A/H7N9 IIV 15 
mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
Notes: N = number of subjects in the safety population in the given stratum; N* = number of subjects in the safety population in the given study group; 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: 17-0090 
Version 1.0 
14JAN2021 
- 92 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.3.1.1 
Solicited Adverse Events 
Table 50: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom, Stratum and 
Study Group, Safety Population 
Symptom 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
n 
% 
95% CI 
n 
% 
95% CI 
n 
% 
95% CI 
n 
% 
95% CI 
n 
% 
95% CI 
n 
% 
95% 
CI 
3.75 mcg A/H7N9 IIV 
Any Symptom 
x 
xx 
xx, xx 
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 
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 
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 
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 
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 
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 
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 
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 
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 
x 
xx 
xx, xx 
Any Injection Site Symptom 
x 
xx 
xx, xx 
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 
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 
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 
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 
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 
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 
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 
x 
xx 
xx, xx 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 93 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
n 
% 
95% CI 
n 
% 
95% CI 
n 
% 
95% CI 
n 
% 
95% CI 
n 
% 
95% CI 
n 
% 
95% 
CI 
Induration/Swelling 
x 
xx 
xx, xx 
x 
xx 
xx, xx 
x 
xx 
xx, xx 
x 
xx 
xx, xx 
x 
xx 
xx, xx 
x 
xx 
xx, xx 
Induration/Swelling 
(measurement) 
x 
xx 
xx, xx 
x 
xx 
xx, xx 
x 
xx 
xx, xx 
x 
xx 
xx, xx 
x 
xx 
xx, xx 
x 
xx 
xx, xx 
3.75 mcg A/H7N9 IIV + AS03 
Any Symptom 
x 
xx 
xx, xx 
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 
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 
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 
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 
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 
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 
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 
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 
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 
x 
xx 
xx, xx 
Any Injection Site Symptom 
x 
xx 
xx, xx 
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 
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 
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 
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 
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 
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 
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 
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 
x 
xx 
xx, xx 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 94 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
n 
% 
95% CI 
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 
x 
xx 
xx, xx 
All Subjects 
Any Symptom 
x 
xx 
xx, xx 
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 
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 
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 
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 
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 
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 
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 
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 
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 
x 
xx 
xx, xx 
Any Injection Site Symptom 
x 
xx 
xx, xx 
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 
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 
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 
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 
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 
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 
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 
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 
x 
xx 
xx, xx 
Induration/Swelling 
(measurement) 
x 
xx 
xx, xx 
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: 17-0090 
Version 1.0 
14JAN2021 
- 95 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
n 
% 
95% CI 
n 
% 
95% CI 
n 
% 
95% CI 
n 
% 
95% CI 
n 
% 
95% CI 
n 
% 
95% 
CI 
Notes: N = Number of subjects in the safety population for the given stratum; n = number of subjects with reported event. 
95% CI estimated using Clopper-Pearson exact method. 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 96 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 51: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity, Stratum and Study Group, 
Safety Population 
Symptom 
Severity 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects  
(N=X) 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
n 
% 
95% 
CI 
3.75 mcg A/H7N9 IIV 
Any Symptom 
None 
x 
xx 
xx-xx 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
x 
xx 
xx-xx 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 97 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
Severity 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects  
(N=X) 
n 
% 
95% 
CI 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
x 
xx 
xx-xx 
Any Injection Site 
Symptom 
None 
x 
xx 
xx-xx 
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: 17-0090 
Version 1.0 
14JAN2021 
- 98 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
Severity 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects  
(N=X) 
n 
% 
95% 
CI 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
xx 
xx-xx 
xx-xx 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 99 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
Severity 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects  
(N=X) 
n 
% 
95% 
CI 
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 
xx 
xx-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 
xx 
xx-xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
xx 
xx-xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
xx 
xx-xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
xx 
xx-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 
xx 
xx-xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
xx 
xx-xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
xx 
xx-xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
xx 
xx-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 
xx 
xx-xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
xx 
xx-xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
xx 
xx-xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
xx 
xx-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 
xx 
xx-xx 
xx-xx 
 
Mild 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
xx 
xx-xx 
xx-xx 
 
Moderate 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
xx 
xx-xx 
xx-xx 
 
Severe 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
x 
xx 
xx-xx 
xx 
xx-xx 
xx-xx 
[repeat for 3.75 mcg A/H7N9 IIV + AS03 and All Subjects] 
Notes: N = Number of subjects in the safety population in the given stratum; n = number of subjects with reported event. 
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: 17-0090 
Version 1.0 
14JAN2021 
- 100 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 52: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Severity, Day Post Vaccination, Stratum and 
Study Group, 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 
% 
3.75 mcg A/H7N9 (N=X) 
All Subjects (N*=X) 
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 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0090 
Version 1.0 
14JAN2021 
- 101 - 
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 
% 
Malaise 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Myalgia 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Arthralgia 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Headache 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nausea 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Any Injection Site Symptom 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pain 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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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 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Erythema (measurement) 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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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 
% 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Induration/Swelling 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Induration/Swelling (measurement) 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for Stratum 1 – 5] 
[repeat for 3.75 mcg A/H7N9 IIV + AS03 (N=X) and All Subjects (N=X)] 
Notes: N = Number of subjects in the safety population in the given study group; N* = Number of subjects in the safety population in the given study group and stratum; n = number of subjects with 
reported event. 
Severity is the maximum severity reported post dosing for each subject for each day. 


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14.3.1.2 
Unsolicited Adverse Events 
Table 53: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events with 95% Confidence Intervals by 
MedDRA System Organ Class and Preferred Term, Stratum and Study Group, Safety Population 
 
 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV 
with MF59/AS03 
then 2013 A/H7N9 
IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects  
(N=X) 
MedDRA System 
Organ Class 
MedDRA 
Preferred Term 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
3.75 mcg A/H7N9 IIV 
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) 
[SOC 1] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
3.75 mcg A/H7N9 IIV + AS03 
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) 
[SOC 1] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
All Subjects 


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2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV 
with MF59/AS03 
then 2013 A/H7N9 
IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects  
(N=X) 
MedDRA System 
Organ Class 
MedDRA 
Preferred Term 
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) 
[SOC 1] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
Notes: N = Number of subjects in the safety population in the given stratum; n = number of subjects with reported event. 
A subject is only counted once per PT. 


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Table 54: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events by MedDRA System Organ Class and Preferred 
Term, Maximum Severity, Relationship, Stratum and Study Group, Safety Population 
MedDRA System Organ Class 
MedDRA Preferred Term 
Any Incidence 
Severitya 
Relationship to Vaccinationb 
Mild 
Moderate 
Severe 
Not Related 
Related 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
3.75 mcg A/H7N9 (N=X) 
All Subjects (N*=X) 
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 Strata 1 - 5] 
[repeat for 3.75 mcg A/H7N9 IIV + AS03 (N=X) and All Subjects (N=X)] 
Notes: N = Number of subjects in the safety population in the given study group; N* = Number of subjects in the safety population in the given study group and stratum; n = number of subjects with 
reported event. 
a For severity, a subject is counted once per preferred term and is summarized according to their highest severity. 
b For relationship, a subject is only counted once per preferred term and is summarized according to their closest relationship. 
 


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Table 55: 
Number and Percentage of Subjects Experiencing Non-Serious Related Unsolicited Adverse Events by MedDRA System Organ 
Class and Preferred Term, Maximum Severity, Stratum and Study Group, Safety Population 
MedDRA System Organ Class 
MedDRA Preferred Term 
Any Incidence 
Severitya 
Mild 
Moderate 
Severe 
n 
% 
n 
% 
n 
% 
n 
% 
3.75 mcg A/H7N9 (N=X) 
All Subjects (N*=X) 
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 Strata 1 - 5] 
[repeat for 3.75 mcg A/H7N9 IIV + AS03 (N=X) and All Subjects (N=X)] 
Notes: N = Number of subjects in the safety population in the given study group; N* = Number of subjects in the safety population in the given study group and stratum; n = number of subjects with 
reported event. 
a For severity, a subject is counted once per preferred term and is summarized according to their highest severity. 
 


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Table 56: 
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, Stratum and Study Group, Safety Population 
 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV 
with MF59/AS03 then 
2013 A/H7N9 IIV 15 
mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
Day 1-8 
Post Vac  
Day 9-22 
Post Vac  
Day 1-8 
Post Vac  
Day 9-22 
Post Vac  
Day 1-8 
Post Vac  
Day 9-22 
Post Vac  
Day 1-8 
Post Vac  
Day 9-22 
Post Vac  
Day 1-8 
Post Vac  
Day 9-22 
Post Vac  
Day 1-8 
Post Vac  
Day 9-22 
Post Vac  
MedDRA System 
Organ Class 
MedDRA 
Preferred Term 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
3.75 mcg A/H7N9 
Any SOC 
Any PT 
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] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[repeat for 3.75 mcg A/H7N9 IIV + AS03 and All Subjects] 
Notes: N = Number of subjects in the safety population in the given stratum; n = number of subjects with reported event. 
For each time period, a subject is only counted once per PT. 
 
 


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Table 57: 
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, Stratum and Study Group, Safety 
Population 
 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV 
with MF59/AS03 then 
2013 A/H7N9 IIV 15 
mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
Day 1-8 
Post Vac  
Day 9-22 
Post Vac  
Day 1-8 
Post Vac  
Day 9-22 
Post Vac  
Day 1-8 
Post Vac  
Day 9-22 
Post Vac  
Day 1-8 
Post Vac  
Day 9-22 
Post Vac  
Day 1-8 
Post Vac  
Day 9-22 
Post Vac  
Day 1-8 
Post Vac  
Day 9-22 
Post Vac  
MedDRA System 
Organ Class 
MedDRA 
Preferred Term 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
3.75 mcg A/H7N9 
Any SOC 
Any PT 
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] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[repeat for 3.75 mcg A/H7N9 IIV + AS03 and All Subjects] 
Notes: N = Number of subjects in the safety population in the given stratum; n = number of subjects with reported event. 
For each time period, a subject is only counted once per PT. 
 
 


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Table 58: 
Number of Unsolicited Adverse Events by MedDRA System Organ Class and Preferred Term, Day Post Vaccination, Stratum 
and Study Group, Safety Population 
 
2013 A/H7N9 IIV + 
MF59  
(N=X) 
2013 A/H7N9 IIV + 
AS03 
(N=X) 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV 
with MF59/AS03 
then 2013 A/H7N9 
IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
Day 1-8 
Post Vac  
Day 9-22 
Post Vac  
Day 1-8 
Post Vac  
Day 9-22 
Post Vac  
Day 1-8 
Post Vac  
Day 9-22 
Post Vac  
Day 1-8 
Post Vac  
Day 9-22 
Post Vac  
Day 1-8 
Post Vac  
Day 9-22 
Post Vac  
Day 1-8 
Post Vac 
Day 9-22 
Post Vac 
MedDRA System 
Organ Class 
MedDRA 
Preferred Term 
Events 
Events 
Events 
Events 
Events 
Events 
Events 
Events 
Events 
Events 
Events 
Events 
3.75 mcg A/H7N9 
Any SOC 
Any PT 
x 
x 
x 
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 3.75 mcg A/H7N9 IIV + AS03 and All Subjects] 
Notes: N = Number of subjects in the safety population in the given stratum. 
 
 


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14.3.2 Listing of Deaths, Other Serious and Significant Adverse Events 
Table 59: 
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 
No. of Days 
Post Vac 
(Duration) 
No. of 
Days Post 
Vac the 
Event 
Became 
Serious 
Reason 
Reported 
as an SAE 
Severity 
Relationship to 
Study 
Treatment 
If Not 
Related, 
Alternative 
Etiology 
Subject 
Withdrew Due 
to AE 
Outcome 
MedDRA 
System 
Organ 
Class 
MedDRA 
Preferred 
Term 
Subject ID: , Study Group: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
Comments: 
Subject ID: , Study Group: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 


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Table 60: 
Listing of Medically Attended Adverse Events, 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 
No. of Days Post 
Vac (Duration) 
Severity 
Relationship to 
Study Treatment 
If Not Related, 
Alternative 
Etiology 
Subject Withdrew 
Due to AE 
Outcome 
MedDRA 
System Organ 
Class 
MedDRA 
Preferred Term 
Subject ID: , Study Group: , AE Number:  
 
 
 
 
 
 
 
 
 
Comments: 
 
 
 
 
 
 
 
 
 
Subject ID: , Study Group: , AE Number:  
 
 
 
 
 
 
 
 
 
Comments: 
Tables with similar format: 
Table 61: 
Listing of New Onset Chronic Medical Conditions, Safety Population 
Table 62: 
Listing of Potentially Immune Mediated Medical Conditions, Safety Population 
Table 63: 
Listing of Non-Serious, Unsolicited, Moderate or Severe Adverse Events, Safety Population 
 


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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) 
 


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14.3.4 Abnormal Laboratory Value Listings (by Subject) 
Table 64: 
Listing of Abnormal Laboratory Results – Chemistry, Safety Population 
Subject 
ID 
Study Group 
Stratum 
Sex 
Age (years) 
Planned 
Time Point 
Actual Study 
Day 
Laboratory 
Parameter 
(Units) 
Result 
(Severity) 
Relationship 
to 
Treatment 
If Not 
Related, 
Alternate 
Etiology 
Subject 
Withdrew 
Due to 
Result? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 65: 
Listing of Abnormal Laboratory Results – Hematology, Safety Population 
Subject 
ID 
Study Group 
Stratum 
Sex 
Age (years) 
Planned 
Time Point 
Actual Study 
Day 
Laboratory 
Parameter 
(Units) 
Result 
(Severity) 
Relationship 
to 
Treatment 
If Not 
Related, 
Alternate 
Etiology 
Subject 
Withdrew 
Due to 
Result? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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14.3.4.5 
Clinical Laboratory Reference Ranges 
(Placeholder for the CSR) 
 


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14.3.5 Displays of Laboratory Results 
14.3.5.1 
Chemistry Results 
Table 66: 
Laboratory Results by Parameter, Maximum Severity, Study Day, Stratum and Study Group – Any Chemistry Parameter, Safety 
Population 
Study Group 
Stratum 
Study Day 
N 
None 
Mild / 
Grade 1 
Moderate/ 
Grade 2 
Severe/ 
Grade 3 
Missing 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
3.75 mcg A/H7N9 IIV 
2013 A/H7N9 IIV + MF59  
 
Baseline 
X 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
2013 A/H7N9 IIV + AS03 
 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
2013 A/H7N9 IIV 15 mcg 
or 45 mcg unadjuvanted  
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
A/H7 IIV-Naive 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 


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Study Group 
Stratum 
Study Day 
N 
None 
Mild / 
Grade 1 
Moderate/ 
Grade 2 
Severe/ 
Grade 3 
Missing 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
All Subjects 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
[repeat for 3.75 mcg A/H7N9 IIV + AS03 and All Subjects] 
Note: N = Number of subjects in the safety population within the given study group and stratum with visit documentation for the corresponding day; n = number of events. 
The “Max Post Baseline” rows indicate the maximum severity experienced by each subject at any time point post baseline, including unscheduled assessments.  
Tables with similar format: 
Table 67: 
Laboratory Results by Parameter, Maximum Severity, Study Day, Stratum and Study Group - Alanine Aminotransferase, Safety 
Population 
Table 68: 
Laboratory Results by Parameter, Maximum Severity, Study Day, Stratum and Study Group - Total Bilirubin, Safety Population 
Table 69: 
Laboratory Results by Parameter, Maximum Severity, Study Day, Stratum and Study Group – Creatinine, Safety Population 


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Table 70: 
Laboratory Summary Statistics by Parameter, Study Day, Stratum and Study Group – Alanine Aminotransferase (IU/L), Safety 
Population 
Study Group 
Stratum 
Study Day 
N 
Mean 
Standard 
Deviation 
Median 
Min, Max 
 
3.75 mcg A/H7N9 IIV 
2013 A/H7N9 IIV + MF59 
Baseline 
x 
xx.x 
xx.x 
xx 
xx, xx 
 
 
Day 8 
 
 
 
 
 
 
2013 A/H7N9 IIV + AS03 
Baseline 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
2013 A/H7N9 IIV 15 mcg or 45 mcg 
unadjuvanted 
Baseline 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
2013 A/H7N9 IIV with MF59/AS03 
then 2013 A/H7N9 IIV 15 mcg 
Baseline 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
A/H7 IIV-Naive 
Baseline 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
All Subjects 
Baseline 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
[Repeat for 3.75 mcg A/H7N9 IIV + AS03 and All Subjects] 
Note: N = Number of subjects in the safety population. 
Tables with similar format: 
Table 71: 
Laboratory Summary Statistics by Parameter, Study Day, Stratum and Study Group – Total Bilirubin (mg/dL), Safety 
Population 
Table 72: 
Laboratory Summary Statistics by Parameter, Study Day, Stratum and Study Group – Creatinine, Safety Population 
 


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14.3.5.2 
Hematology Results 
Table 73: 
Laboratory Results by Parameter, Maximum Severity, Study Day, Stratum and Study Group – Any Hematology Parameter, 
Safety Population 
Study Group 
Stratum 
Study Day 
N 
None 
Mild / 
Grade 1 
Moderate/ 
Grade 2 
Severe/ 
Grade 3 
Missing 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
3.75 mcg A/H7N9 IIV 
2013 A/H7N9 IIV + MF59 
Baseline 
X 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
2013 A/H7N9 IIV + AS03 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
2013 A/H7N9 IIV 15 mcg 
or 45 mcg unadjuvanted  
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
A/H7 IIV-Naive 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
All Subjects 
Baseline 
 
 
 
 
 
 
 
 
 
 
 


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Study Group 
Stratum 
Study Day 
N 
None 
Mild / 
Grade 1 
Moderate/ 
Grade 2 
Severe/ 
Grade 3 
Missing 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
[repeat for 3.75 mcg A/H7N9 IIV + AS03 and All Subjects] 
Note: N = Number of subjects in the safety population within the given study group and stratum with visit documentation for the corresponding day. 
The “Max Post Baseline” rows indicate the maximum severity experienced by each subject at any time point post baseline, including unscheduled assessments. 
Table with similar format: 
Table 74: 
Laboratory Results by Parameter, Maximum Severity, Study Day, Stratum and Study Group – Hemoglobin, Safety Population 


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Table 75: 
Laboratory Results by Parameter, Maximum Severity, Study Day, Stratum and Study Group – White Blood Cells (103/µL), 
Safety Population 
Study Group 
Stratum 
Study Day 
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 
% 
3.75 mcg 
A/H7N9 IIV 
2013 A/H7N9 IIV + 
MF59 
Baseline  
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity 
Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2013 A/H7N9 IIV + 
AS03 
Baseline  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity 
Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted  
Baseline  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity 
Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg  
Baseline  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity 
Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A/H7 IIV-Naive 
Baseline  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity 
Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Study Group 
Stratum 
Study Day 
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 
% 
 
All Subjects 
Baseline  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity 
Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[repeat for 3.75 mcg A/H7N9 IIV + AS03] 
Note: N = Number of subjects in the safety population within the given study group and stratum with visit documentation for the corresponding day. 
The “Max Post Baseline” rows indicate the maximum severity experienced by each subject at any time point post baseline, including unscheduled assessments. 
Table with similar format: 
Table 76: 
Laboratory Results by Parameter, Maximum Severity, Study Day, Stratum and Study Group – Platelets (103/µL), Safety 
Population 
 


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Table 77: 
Laboratory Summary Statistics by Parameter, Study Day, Stratum and Study Group – Hemoglobin (g/dL), Safety Population 
Study Group 
Stratum 
Study Day 
N 
Mean 
Standard 
Deviation 
Median 
Min, Max 
 
3.75 mcg A/H7N9 IIV 
2013 A/H7N9 IIV + MF59 
Baseline 
x 
xx.x 
xx.x 
xx 
xx, xx 
 
 
Day 8 
 
 
 
 
 
 
2013 A/H7N9 IIV + AS03  
 
Baseline 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
2013 A/H7N9 IIV 15 mcg or 45 mcg 
unadjuvanted 
 
Baseline 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
2013 A/H7N9 IIV with MF59/AS03 
then 2013 A/H7N9 IIV 15 mcg  
Baseline 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
A/H7 IIV-Naive 
Baseline 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
 
All Subjects 
Baseline 
 
 
 
 
 
 
 
Day 8 
 
 
 
 
 
[Repeat for 3.75 mcg A/H7N9 IIV + AS03 and All Subjects] 
Note: N = Number of subjects in the safety population 
Tables with similar format: 
Table 78: 
Laboratory Summary Statistics by Parameter, Study Day, Stratum and Study Group – White Blood Cells (103/µL), Safety 
Population 
Table 79: 
Laboratory Summary Statistics by Parameter, Study Day, Stratum and Study Group – Platelets (103/µL), Safety Population 
 


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14.3.6 Displays of Vital Signs 
Table 80: 
Vital Signs by Assessment, Maximum Severity, Study Day, Stratum and Study Group – Any Assessment, Safety Population 
Study Group 
Stratum 
Study Day 
N 
None 
Mild 
Moderate 
Severe 
Missing 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
3.75 mcg A/H7N9 IIV 
2013 A/H7N9 IIV + MF59 
Baseline 
X 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
2013 A/H7N9 IIV + AS03 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
2013 A/H7N9 IIV 15 mcg 
or 45 mcg unadjuvanted 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
A/H7 IIV-Naive 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
All Subjects 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
[repeat for 3.75 mcg A/H7N9 IIV + AS03 and All Subjects] 
Note: N = Number of subjects in the safety population within the given study group and stratum with visit documentation for the corresponding day. 
The “Max Post Baseline” rows indicate the maximum severity experienced by each subject at any time point post baseline, including unscheduled assessments. 
 
 


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Table with similar format: 
Table 81: 
Vital Signs by Assessment, Maximum Severity, Study Day, Stratum and Study Group - Oral Temperature, Safety Population 
 


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Table 82: 
Vital Signs by Assessment, Maximum Severity, Study Day, Stratum and Study Group – Systolic Blood Pressure, Safety 
Population 
Study Group 
Stratum 
Study Day 
N 
None 
Mild 
(Low) 
Mild 
(High) 
Moderate 
(Low) 
Moderate 
(High) 
Severe 
(Low) 
Severe 
(High) 
Missing 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
3.75 mcg 
A/H7N9 IIV 
2013 A/H7N9 IIV + 
MF59 
Baseline  
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
 
Max Severity 
Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2013 A/H7N9 IIV + 
AS03 
Baseline  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity 
Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2013 A/H7N9 IIV 15 
mcg or 45 mcg 
unadjuvanted 
Baseline  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity 
Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2013 A/H7N9 IIV with 
MF59/AS03 then 2013 
A/H7N9 IIV 15 mcg 
Baseline  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity 
Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A/H7 IIV-Naive 
Baseline  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity 
Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All Subjects 
Baseline  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity 
Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[repeat for 3.75 mcg A/H7N9 IIV + AS03 and All Subjects] 
Note: N = Number of subjects in the safety population within the given study group and stratum with visit documentation for the corresponding day. 
The “Max Post Baseline” rows indicate the maximum severity experienced by each subject at any time point post baseline, including unscheduled assessments. 
 
 


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Tables with similar format: 
Table 83: 
Vital Signs by Assessment, Maximum Severity, Study Day, Stratum and Study Group - Diastolic Blood Pressure, Safety 
Population 
Table 84: 
Vital Signs by Assessment, Maximum Severity, Study Day, Stratum and Study Group - Pulse, Safety Population 
 


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14.4 
Summary of Concomitant Medications 
Table 85: 
Number and Percentage of Subjects with Prior and Concurrent Medications by WHO Drug Classification, Stratum and Study 
Group, Safety Population 
WHO Drug Code 
Level 1, Anatomic Group 
WHO Drug Code 
Level 2, Therapeutic 
Subgroup 
2013 A/H7N9 IIV 
+ MF59  
(N=X) 
2013 A/H7N9 IIV 
+ AS03 
(N=X) 
2013 A/H7N9 IIV 
15 mcg or 45 mcg 
unadjuvanted 
(N=X) 
2013 A/H7N9 IIV 
with MF59/AS03 
then 2013 A/H7N9 
IIV 15 mcg  
(N=X) 
A/H7 IIV Naïve 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
3.75 mcg A/H7N9 IIV (N*=X) 
Any Level 1 Codes 
Any Level 2 Codes 
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] 
 
 
 
 
 
 
 
 
 
 
 
 
[repeat for 3.75 mcg A/H7N9 IIV + AS03 (N*=X) and All Subjects (N*=X)] 
Notes: N = Number of subjects in the safety population in the given stratum; N* = Number of subjects in the safety population in the given study group; 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 
 
 


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LIST OF FIGURES 
Figure 1: 
CONSORT Flow Diagram .......................................................................................133 
Figure 2: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody 
against A/Hong Kong/125/2017 (H7N9) by Study Day, Stratum and Study 
Group, Modified Intent-to-Treat Population ............................................................134 
Figure 3: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody 
against A/Hong Kong/125/2017 (H7N9) by Study Day, Stratum and Study 
Group, Per-Protocol Population................................................................................135 
Figure 4: 
Reverse Cumulative Distribution of Neutralizing Antibody against A/Hong 
Kong/125/2017 (H7N9) by Study Day, Stratum and Study Group, Modified 
Intent-to-Treat Population ........................................................................................135 
Figure 5: 
Reverse Cumulative Distribution of Neutralizing Antibody against A/Hong 
Kong/125/2017 (H7N9) by Study Day, Stratum and Study Group, Per-
Protocol Population ..................................................................................................135 
Figure 6: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody 
against A/Shanghai/2/2013 (H7N9) by Study Day, Stratum and Study 
Group, Per-Protocol Population................................................................................135 
Figure 7: 
Reverse Cumulative Distribution of Neutralizing Antibody against 
A/Shanghai/2/2013 (H7N9) by Study Day, Stratum and Study Group, Per-
Protocol Population ..................................................................................................135 
Figure 8: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody 
against A/Guangdong/17F003/2016 (H7N9) by Study Day, Stratum and 
Study Group, Per-Protocol Population .....................................................................135 
Figure 9: 
Reverse Cumulative Distribution of Neutralizing Antibody against 
A/Guangdong/17F003/2016 (H7N9) by Study Day, Stratum and Study 
Group, Per-Protocol Population................................................................................135 
Figure 10: Geometric Mean Titers of Hemagglutination Inhibition Antibody Against 
A/Hong Kong/125/2017 (H7N9) by Study Day, Stratum and Study Group, 
Modified Intent-to-Treat Population .........................................................................136 
Figure 11: Geometric Mean Titers of Hemagglutination Inhibition Antibody against 
A/Hong Kong/125/2017 (H7N9) by Study Day, Stratum and Study Group, 
Per-Protocol Population ............................................................................................136 
Figure 12: Geometric Mean Titers of Neutralizing Antibody against A/Hong 
Kong/125/2017 (H7N9) by Study Day, Stratum and Study Group, Modified 
Intent-to-Treat Population ........................................................................................136 
Figure 13: Geometric Mean Titers of Neutralizing Antibody against A/Hong 
Kong/125/2017 (H7N9) by Study Day, Stratum and Study Group, Per-
Protocol Population ..................................................................................................136 


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Figure 14: Geometric Mean Titers of Hemagglutination Inhibition Antibody against 
A/Shanghai/2/2013 (H7N9) by Study Day, Stratum and Study Group, Per-
Protocol Population ..................................................................................................136 
Figure 15: Geometric Mean Titers of Neutralizing Antibody against A/Shanghai/2/2013 
(H7N9) by Study Day, Stratum and Study Group, Per-Protocol Population ...........136 
Figure 16: Geometric Mean Titers of Hemagglutination Inhibition Antibody against 
A/Guangdong/17F003/2016 (H7N9) by Study Day, Stratum and Study 
Group, Per-Protocol Population................................................................................136 
Figure 17: Geometric Mean Titers of Neutralizing Antibody against 
A/Guangdong/17F003/2016 (H7N9) by Study Day, Stratum and Study 
Group, Per-Protocol Population................................................................................136 
Figure 18: Correlation of Hemagglutination Inhibition Antibody and Neutralizing 
Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Day, Stratum 
and Study Group, Modified Intent-to-Treat Population ...........................................137 
Figure 19: Correlation of Hemagglutination Inhibition Antibody and Neutralizing 
Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Day, Stratum 
and Study Group, Per-Protocol Population ..............................................................138 
Figure 20: Correlation of Hemagglutination Inhibition Antibody and Neutralizing 
Antibody Against A/Shanghai/2/2013 (H7N9) by Study Day, Stratum and 
Study Group, Per-Protocol Population .....................................................................138 
Figure 21: Correlation of Hemagglutination Inhibition Antibody and Neutralizing 
Antibody Against A/Guangdong/17F003/2016 (H7N9) by Study Day, 
Stratum and Study Group, Per-Protocol Population .................................................138 
Figure 22: Correlation of A/Hong Kong/125/2017 (H7N9) and A/Shanghai/2/2013 
(H7N9) Hemagglutination Inhibition Antibody Results by Study Day, 
Stratum and Study Group, Per-Protocol Population .................................................138 
Figure 23: Correlation of A/Hong Kong/125/2017 (H7N9) and A/Shanghai/2/2013 
(H7N9) Neutralizing Antibody Results by Study Day, Stratum and Study 
Group, Per-Protocol Population................................................................................138 
Figure 24: Correlation of A/Hong Kong/125/2017 (H7N9) and 
A/Guangdong/17F003/2016 (H7N9) Hemagglutination Inhibition Antibody 
Results by Study Day, Stratum and Study Group, Per-Protocol Population ............138 
Figure 25: Correlation of A/Hong Kong/125/2017 (H7N9) and 
A/Guangdong/17F003/2016 (H7N9) Hemagglutination Inhibition Antibody 
Results by Study Day, Stratum and Study Group, Per-Protocol Population ............138 
Figure 26: Maximum Severity of Solicited Systemic Symptoms per Subject by Day 
Post Vaccination, Stratum and Study Group, Safety Population ..............................139 
Figure 27: Maximum Severity of Solicited Injection Site Symptoms per Subject by Day 
Post Vaccination, Stratum and Study Group, Safety Population ..............................139 


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Figure 28: Frequency of Related Adverse Events by MedDRA System Organ Class, 
Severity, Stratum and Study Group, Safety Population ...........................................140 
Figure 29: Incidence of Related Adverse Events by MedDRA® System Organ Class, 
Maximum Severity, Stratum and Study Group, Safety Population ..........................141 
Figure 30: Frequency of Adverse Events by MedDRA System Organ Class, 
Relationship to Vaccination, Stratum and Study Group, Safety Population ............142 
Figure 31: Incidence of Adverse Events by MedDRA System Organ Class, Relationship 
to Vaccination, Stratum and Study Group, Safety Population .................................143 
Figure 32: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Laboratory Parameter, Stratum and Study Group – Alanine 
Aminotransferase, Safety Population .......................................................................144 
Figure 33: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Laboratory Parameter, Stratum and Study Group – Total Bilirubin, Safety 
Population .................................................................................................................144 
Figure 34: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Laboratory Parameter, Stratum and Study Group – Creatinine, Safety 
Population .................................................................................................................144 
Figure 35: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Laboratory Parameter, Stratum and Study Group – Hemoglobin, Safety 
Population .................................................................................................................145 
Figure 36: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Laboratory Parameter, Stratum and Study Group – White Blood Cells, 
Safety Population ......................................................................................................145 
Figure 37: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Laboratory Parameter, Stratum and Study Group – Platelets, Safety 
Population .................................................................................................................145 
 


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10.1 
Disposition of Subjects 
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) 
♦[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) 
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) 
♦[Reason 1] (x), [Reason 2] (x) 
Discontinued Intervention (n=x) 
♦[Reason 1] (x), [Reason 2] (x) 
Early Termination (n=32) 
♦[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) 
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 Response Figures 
Figure 2: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
A/Hong Kong/125/2017 (H7N9) by Study Day, Stratum and Study Group, 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 1, Day 8, Day 22, Day 181). 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 be either a dashed or solid line with different color and markers used to distinguish strata.] 
 
 
 
 
Reverse Cumulative Distribution Curves
Hemagglutination Titer
A/New Caledonia/20/99
Pre-Vaccination
IVV without IFN
 IVV with 1M IFN
 IVV with 10M IFN
Cumulative Percent
0
10
20
30
40
50
60
70
80
90
100
TITER
1.4
4
8
16
32
64
128
256
512
1280
2048
4096
Reverse Cumulative Distribution Curves
Hemagglutination Titer
A/New Caledonia/20/99
14 Days Post Vaccination
IVV without IFN
 IVV with 1M IFN
 IVV with 10M IFN
Cumulative Percent
0
10
20
30
40
50
60
70
80
90
100
TITER
1.4
4
8
16
32
64
128
256
512
1280
2048
4096
Reverse Cumulative Distribution Curves
Hemagglutination Titer
A/New Caledonia/20/99
28 Days Post Vaccination
IVV without IFN
 IVV with 1M IFN
 IVV with 10M IFN
Cumulative Percent
0
10
20
30
40
50
60
70
80
90
100
TITER
1.4
4
8
16
32
64
128
256
512
1280
2048
4096


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Figures with similar format: 
Figure 3: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
A/Hong Kong/125/2017 (H7N9) by Study Day, Stratum and Study Group, Per-Protocol 
Population 
Figure 4: 
Reverse Cumulative Distribution of Neutralizing Antibody against A/Hong 
Kong/125/2017 (H7N9) by Study Day, Stratum and Study Group, Modified Intent-to-
Treat Population 
Figure 5: 
Reverse Cumulative Distribution of Neutralizing Antibody against A/Hong 
Kong/125/2017 (H7N9) by Study Day, Stratum and Study Group, Per-Protocol 
Population 
Figure 6: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
A/Shanghai/2/2013 (H7N9) by Study Day, Stratum and Study Group, Per-Protocol 
Population 
Figure 7: 
Reverse Cumulative Distribution of Neutralizing Antibody against A/Shanghai/2/2013 
(H7N9) by Study Day, Stratum and Study Group, Per-Protocol Population 
Figure 8: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
A/Guangdong/17F003/2016 (H7N9) by Study Day, Stratum and Study Group, Per-
Protocol Population 
Figure 9: 
Reverse Cumulative Distribution of Neutralizing Antibody against 
A/Guangdong/17F003/2016 (H7N9) by Study Day, Stratum and Study Group, Per-
Protocol Population 


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Figure 10: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody Against A/Hong 
Kong/125/2017 (H7N9) by Study Day, Stratum and Study Group, 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 open/closed markers and dashed/solid 
lines, with separate color and marker shape used to distinguish strata] 
 
Figures with similar format: 
Figure 11: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody against A/Hong 
Kong/125/2017 (H7N9) by Study Day, Stratum and Study Group, Per-Protocol 
Population 
Figure 12: 
Geometric Mean Titers of Neutralizing Antibody against A/Hong Kong/125/2017 (H7N9) 
by Study Day, Stratum and Study Group, Modified Intent-to-Treat Population 
Figure 13: 
Geometric Mean Titers of Neutralizing Antibody against A/Hong Kong/125/2017 (H7N9) 
by Study Day, Stratum and Study Group, Per-Protocol Population 
Figure 14: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody against 
A/Shanghai/2/2013 (H7N9) by Study Day, Stratum and Study Group, Per-Protocol 
Population 
Figure 15: 
Geometric Mean Titers of Neutralizing Antibody against A/Shanghai/2/2013 (H7N9) by 
Study Day, Stratum and Study Group, Per-Protocol Population 
Figure 16: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody against 
A/Guangdong/17F003/2016 (H7N9) by Study Day, Stratum and Study Group, Per-
Protocol Population 
Figure 17: 
Geometric Mean Titers of Neutralizing Antibody against A/Guangdong/17F003/2016 
(H7N9) by Study Day, Stratum and Study Group, Per-Protocol Population 
 
 


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Figure 18: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody Against 
A/Hong Kong/125/2017 (H7N9) by Study Day, Stratum and Study Group, 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 (Day 1, Day 8, Day 22, D181). 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 separate 
color, with marker shape used to distinguish strata. The spearman correlation should be calculated over all 
subjects and annotated within each panel as “Spearman Correlation (r=0.xx, p=0.xx)”] 
 
 
 


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Figures with similar format: 
Figure 19: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody Against 
A/Hong Kong/125/2017 (H7N9) by Study Day, Stratum and Study Group, Per-Protocol 
Population 
Figure 20: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody Against 
A/Shanghai/2/2013 (H7N9) by Study Day, Stratum and Study Group, Per-Protocol 
Population 
Figure 21: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody Against 
A/Guangdong/17F003/2016 (H7N9) by Study Day, Stratum and Study Group, Per-
Protocol Population 
Figure 22: 
Correlation of A/Hong Kong/125/2017 (H7N9) and A/Shanghai/2/2013 (H7N9) 
Hemagglutination Inhibition Antibody Results by Study Day, Stratum and Study Group, 
Per-Protocol Population 
Figure 23: 
Correlation of A/Hong Kong/125/2017 (H7N9) and A/Shanghai/2/2013 (H7N9) 
Neutralizing Antibody Results by Study Day, Stratum and Study Group, Per-Protocol 
Population 
Figure 24: 
Correlation of A/Hong Kong/125/2017 (H7N9) and A/Guangdong/17F003/2016 (H7N9) 
Hemagglutination Inhibition Antibody Results by Study Day, Stratum and Study Group, 
Per-Protocol Population 
Figure 25: 
Correlation of A/Hong Kong/125/2017 (H7N9) and A/Guangdong/17F003/2016 (H7N9) 
Neutralizing Antibody Results by Study Day, Stratum and Study Group, Per-Protocol 
Population


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14.3.1.1 
Solicited Adverse Events 
Figure 26: 
Maximum Severity of Solicited Systemic Symptoms per Subject by Day Post Vaccination, 
Stratum and Study Group, Safety Population 
[Implementation Note: A Generic figure is shown below. A horizontal bar chart should be presented in 3 
image files (each study group and overall) with separate panels for each stratum (6 panels (each stratum and 
all subjects) split into 3 columns and 2 rows). Axes should be labeled as follows: x-axis label: Study Day, y-
axis label: Percentage of Subjects (%). The study groups should be indicated in the panel headers including 
“(N=X)”, where N = the number of subjects 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 27: 
Maximum Severity of Solicited Injection Site Symptoms per Subject by Day Post 
Vaccination, Stratum and Study Group, Safety Population 
 


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14.3.1.2 
Unsolicited Adverse Events 
Figure 28: 
Frequency of Related Adverse Events by MedDRA System Organ Class, Severity, 
Stratum and Study Group, Safety Population 
[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 (each study group and overall) with 
separate panels for each stratum (6 panels (each stratum and all subjects) split into 3 columns and 2 rows). 
Axes should be labeled as follows: y-axis label: System Organ Class, y-axis label: Number of Events. The 
strata should be indicated in the panel headers including “(N=X)”, where N = the number of subjects 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 29: 
Incidence of Related Adverse Events by MedDRA® System Organ Class, Maximum 
Severity, Stratum and Study Group, Safety Population 
[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 (each study group and overall) with 
separate panels for each stratum (6 panels (each stratum and all subjects) split into 3 columns and 2 rows). 
Axes should be labeled as follows: y-axis label: System Organ Class, x-axis label: Percentage of Subjects (%). 
The strata should be indicated in the panel headers including “(N=X)”, where N = the number of subjects 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 30: 
Frequency of Adverse Events by MedDRA System Organ Class, Relationship to 
Vaccination, Stratum and Study Group, Safety Population 
[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 (each study group and overall) with 
separate panels for each stratum (6 panels (each stratum and all subjects) split into 3 columns and 2 rows). 
Axes should be labeled as follows: y-axis label: System Organ Class, y-axis label: Number of Events. The 
strata should be indicated in the panel headers including “(N=X)”, where N = the number of subjects 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 31: 
Incidence of Adverse Events by MedDRA System Organ Class, Relationship to 
Vaccination, Stratum and Study Group, Safety Population 
[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 (each study group and overall) with 
separate panels for each stratum (6 panels (each stratum and all subjects) split into 3 columns and 2 rows). 
Axes should be labeled as follows: y-axis label: System Organ Class, x-axis label: Percentage of Subjects (%). 
The strata should be indicated in the panel headers including “(N=X)”, where N = the number of subjects 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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14.3.5.1 Displays of Laboratory Results - Chemistry 
Figure 32: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Laboratory Parameter, Stratum and Study Group – Alanine Aminotransferase, Safety 
Population 
[Implementation note: A generic figure is shown below. Plot should be generated with all study groups in a 
single image file with panels for each study group and strata (5 rows (strata) x 2 columns (study groups)) with 
a box plot shown for each post-baseline study day that labs are drawn (D8). 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 33: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Laboratory Parameter, Stratum and Study Group – Total Bilirubin, Safety Population 
Figure 34: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Laboratory Parameter, Stratum and Study Group – Creatinine, Safety Population 


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14.3.5.2 Displays of Laboratory Results - Hematology 
Figure 35: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Laboratory Parameter, Stratum and Study Group – Hemoglobin, Safety Population 
[Implementation note: A generic figure is shown below. Plot should be generated with all study groups in a 
single image file with panels for each study group and strata (5 rows (strata) x 2 columns (study groups)) with 
a box plot shown for each post-baseline study day that labs are drawn (D8). 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 36: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Laboratory Parameter, Stratum and Study Group – White Blood Cells, Safety 
Population 
Figure 37: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Laboratory Parameter, Stratum and Study Group – Platelets, Safety Population 
 


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APPENDIX 3. LISTINGS MOCK-UPS 
 
 


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LISTINGS 
Listing 1 
16.1.6 - Listing of Subjects Receiving Investigational Product ...............................148 
Listing 2 
16.2.1 - Early Terminated Subjects ..........................................................................149 
Listing 3 
16.2.2.1 - Subject-Specific Protocol Deviations .......................................................150 
Listing 4 
16.2.2.2 - Non-Subject-Specific Protocol Deviations ..............................................151 
Listing 5 
16.2.3 - Subjects Excluded from Analysis Populations ............................................152 
Listing 6 
16.2.4.1: Demographic Data .....................................................................................153 
Listing 7 
16.2.4.2: Pre-Existing and Concurrent Medical Conditions .....................................154 
Listing 8 
16.2.5: Compliance and/or Drug Concentration Data ..............................................155 
Listing 9 
16.2.6.1 - Individual Efficacy/Immunogenicity Response Data – 
Hemagglutination Inhibition Antibody Results ........................................................156 
Listing 10 16.2.6.2 - Individual Efficacy/Immunogenicity Response Data – 
Neutralizing Antibody Results .................................................................................156 
Listing 11 16.2.7.1 - Solicited Events – Systemic Symptoms ...................................................157 
Listing 12 16.2.7.2: Solicited Events – Injection Site Symptoms..............................................158 
Listing 13 16.2.7.3: Unsolicited Adverse Events .......................................................................159 
Listing 14 16.2.8.1: Clinical Laboratory Results – Chemistry ..................................................160 
Listing 15 16.2.8.2: Clinical Laboratory Results – Hematology ...............................................161 
Listing 16 16.2.9.1: Vital Signs .................................................................................................162 
Listing 17 16.2.9.2: Physical Exam Findings ............................................................................163 
Listing 18 16.2.10: Concomitant Medications ...........................................................................164 
Listing 19 16.2.11.1: Pregnancy Reports – Maternal Information ............................................165 
Listing 20 16.2.11.2: Pregnancy Reports – Gravida and Para ...................................................165 
Listing 21 16.2.11.3: Pregnancy Reports – Live Birth Outcomes .............................................166 
Listing 22 16.2.11.4: Pregnancy Reports – Still Birth Outcomes ..............................................166 
Listing 23 16.2.11.5: Pregnancy Reports – Spontaneous, Elective, or Therapeutic 
Abortion Outcomes ...................................................................................................166 
 
 


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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  
Study Group 
Stratum 
Product Received Study Vaccination 1 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2 
Database Listings by Subject 
16.2.1 Discontinued Subjects 
Listing 2 
16.2.1 - Early Terminated Subjects 
[Implementation Note: In the “Reason” column, concatenate any “specify” fields, including AE number and DV number.] 
Study Group 
Stratum 
Subject ID 
Reason for Early Termination 
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.”] 
Study 
Group 
Stratum 
Subject ID 
DV 
Number 
Deviation 
Deviation 
Category 
Study Day 
Reason for 
Deviation 
Deviation 
Resulted 
in AE? 
Deviation 
Resulted in 
Subject 
Termination? 
Deviation 
Affected 
Product 
Stability? 
Deviation 
Resolution 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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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 
Start Date  
Deviation 
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 Efficacy 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 Study Group” table. The reasons included here 
should match the SAP text that describes who will be excluded from analyses.] 
Study Group 
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: Demographic Data 
[Implementation Note: If a subject is multi-racial, in “Race” column, note “Multiple: (list races, separated by a comma).”] 
Study Group 
 Stratum 
Subject ID 
Sex 
Age at Enrollment 
(years) 
Ethnicity 
Race 
BMI 
Seasonal 
Influenza 
Received 
(2017-2018) 
Seasonal 
Influenza 
Received 
(2018-2019) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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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 
Study 
Group 
Stratum 
 Subject ID 
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) 
Listing 8 
16.2.5: Compliance and/or Drug Concentration Data 
Not applicable for this study. 
 


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16.2.6 Individual Efficacy/Immunogenicity Response Data 
Listing 9 
16.2.6.1 - Individual Efficacy/Immunogenicity Response Data – Hemagglutination Inhibition Antibody Results 
Study Group  
Stratum 
Subject ID  
Planned Study Day 
Actual Study Day 
Strain 
Titer Replicate 1 
Titer Replicate 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing with similar format: 
Listing 10 
16.2.6.2 - Individual Efficacy/Immunogenicity Response Data – Neutralizing Antibody Results 
 
 


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16.2.7 Adverse Events 
Listing 11 
16.2.7.1 - Solicited Events – Systemic Symptoms 
Study Group  
Stratum 
Subject ID  
Post Vac Day 
Assessmenta 
Symptom 
Severity 
Attributed to 
Alternate 
Etiology?b 
Alternate 
Etiology 
 
 
 
 
MA 
 
 
 
 
 
 
 
 
Clinic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: a MA = Data reported by subject on the Memory Aid and reviewed by clinic staff and reported in Solicited Events eCRF. 
b Grade 3 events only. 
Clinic = Data collected by clinic staff during physical exam or symptom assessment (treatment administration record, in-clinic assessment, etc.) 
 
 


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Listing 12 
16.2.7.2: Solicited Events – Injection Site Symptoms 
Study Group  
Stratum 
Subject ID  
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. 
b Grade 3 events only. 
Note: Clinic = Data collected by clinic staff during physical exam or symptom assessment (treatment administration record, in-clinic assessment, etc.) 


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Listing 13 
16.2.7.3: Unsolicited Adverse Events 
Adverse Event 
No. of Days 
Post Vac 
(Duration) 
Severity 
SAE? 
Relationship to 
Study Treatment 
In Not Related, 
Alternative 
Etiology 
Subject 
Terminated 
Due to AE 
Outcome 
MedDRA 
System Organ 
Class 
MedDRA 
Preferred 
Term 
Treatment Group: , Subject ID: , AE Number:  
 
 
 
 
 
 
 
 
 
 
Comments: 
 
 
 
 
 
 
 
 
 
 
Treatment Group: , Subject ID: , AE Number:  
 
 
 
 
 
 
 
 
 
 
Comments: 
Note: For additional details about SAEs, see Table: xx. 
 


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16.2.8 Individual Laboratory Measurements 
Listing 14 
16.2.8.1: Clinical Laboratory Results – Chemistry 
[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.] 
Study 
Group 
Stratum 
Subject ID 
Planned 
Study Day  
Actual 
Study 
Day  
Sex  
Age (years) 
Laboratory 
Parameter (Units) 
Result 
(Severity) 
Reference 
Range Low 
Reference 
Range High 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 15 
16.2.8.2: Clinical Laboratory Results – Hematology 
Study 
Group 
Stratum 
Subject ID 
Planned 
Study 
Day 
Actual 
Study 
Day  
Sex  
Age 
(years) 
Laboratory 
Parameter (Units) 
Result (Severity) 
Reference 
Range Low 
Reference 
Range High 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.9 Vital Signs and Physical Exam Findings 
Listing 16 
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).] 
Study 
Group 
Stratum 
Subject ID 
Planned 
Study Day 
Actual 
Study Day 
Temperature 
(°C) 
Systolic Blood 
Pressure 
(mmHg) 
Diastolic Blood 
Pressure 
(mmHg) 
Heart Rate 
(beats/min) 
Weight 
(kg) 
Height 
(cm) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 17 
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 Description and Number in parentheses, e.g., “Yes 
(AE; 001)”.] 
Study 
Group 
Stratum 
Subject ID 
Planned 
Study Day 
Actual 
Study Day 
Body System 
Abnormal Finding 
Reported as an AE? 
(AE Description; 
Number) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.10 Concomitant Medications 
Listing 18 
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 Description and 
Number in parentheses, e.g., “Yes (AE; 001)”.] 
Study 
Group 
Stratum 
Subject ID 
CM 
Number 
Medication 
Medication Start 
Day 
Medication End 
Day 
Indication 
Taken for an AE? 
(AE Description; 
Number) 
Taken for a condition on 
Medical History? 
(MH Description; 
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 19 
16.2.11.1: Pregnancy Reports – Maternal Information 
Study 
Group 
Stratum 
Subject 
ID  
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 
(LB) 
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. 
Listing 20 
16.2.11.2: Pregnancy Reports – Gravida and Para 
 
 
 
Live Births 
 
 
 
 
 
Subject 
ID 
Pregnancy 
Number 
Gravida 
Extremely 
PBa 
Very 
Early 
PBa 
Early 
PBa 
Late 
PBa 
Early 
TBb 
Full 
TBb 
Late 
TBb 
Post 
TBb 
Still 
Births 
Spontaneous 
Abortion/ 
Miscarriage 
Elective 
Abortions 
Therapeutic 
Abortions 
Major 
Congenital 
Anomaly 
with 
Previous 
Pregnancy? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Gravida includes the current pregnancy, para events do not. 
a Preterm Birth 
b Term Birth 
 
 


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Listing 21 
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 (weeks) 
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 22 
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 (weeks) 
Size for 
Gestational 
Age 
Cord pH 
Congenital 
Anomalies? 
Autopsy 
Performed? 
If Autopsy, Etiology 
for Still Birth 
Identified? 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 23 
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 (weeks) 
Abnormality in Product of Conception? 
Reason for Therapeutic 
Abortion