Clinical trial NCT03318315
Conditions: Avian Influenza Influenza Influenza Immunisation
Keywords: AS03-adjuvanted Inactivated Influenza Vaccine Co-Administered Healthy Adults Immunogenicity Inactivated Seasonal Influenza Vaccine Phase II Safety
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2018-02-20; Completion date: 2019-07-25
Enrollment: 149 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a randomized, un-blinded, Phase II study in males and non-pregnant females, who are in good health, 19 to 64 years of age. This study is designed to assess the safety, reactogenicity, and immunogenicity of a pre-pandemic AS03 (GSK) adjuvanted 2017 monovalent inactivated influenza A/H7N9 vaccine, when two doses are administered 21 days apart either sequentially or simultaneously (within 15 minutes) with licensed seasonal influenza vaccine. Subjects will be randomized into one of three treatment groups. The study will enroll approximately 150 individuals who have no history of influenza A/H7N9 infection or prior receipt of an influenza virus H7 subtype vaccine. Study duration is approximately 16 months with subject participation duration of approximately 13 months. The primary objectives of this study are: 1) to assess the safety and reactogenicity following sequential or simultaneous IM administration of 2 doses of AS03-adjuvanted 2017 H7N9 IIV and one dose of seasonal influenza vaccine (IIV4); 2) to assess the serum HAI and Neut antibody responses against A/H7N9 at approximately 21 days following receipt of two doses of AS03-adjuvanted 2017 H7N9 IIV administered IM approximately 21 days apart; 3) to assess the serum HAI and Neut antibody responses against the seasonal influenza strains at approximately 21 days following receipt of IIV4.

Detailed description:
This is a randomized, un-blinded, Phase II study in males and non-pregnant females, who are in good health, 19 to 64 years of age. This clinical trial is designed to assess the safety, reactogenicity, and immunogenicity of a pre-pandemic AS03 (GSK) adjuvanted 2017 monovalent inactivated influenza A/H7N9 vaccine (2017 H7N9 IIV) manufactured by Sanofi Pasteur (3.75 mcg of HA per dose with Phosphate Buffered Saline (PBS) diluent), when two doses are administered 21 days apart either sequentially or simultaneously (within 15 minutes) with licensed seasonal influenza vaccine. Subjects will be randomized into one of three treatment groups. Group 1 will receive two doses of AS03-adjuvanted 2017 H7N9 IIV, each dose administered IM approximately 21 days apart, and one dose of licensed seasonal IIV4 will be administered IM simultaneously (within 15 minutes) with the first dose of AS03 adjuvanted 2017 H7N9 IIV. Group 2 will receive one dose of IIV4 approximately 21 days prior to the IM administration of two doses of AS03-adjuvanted 2017 H7N9 IIV; each dose of AS03-adjuvanted 2017 H7N9 IIV will be given approximately 21 days apart. Group 3 will receive one dose IM of IIV4 as an un-blinded comparator. The study will enroll approximately 150 individuals who have no history of influenza A/H7N9 infection or prior receipt of an influenza virus H7 subtype vaccine. Study duration is approximately 16 months with subject participation duration of approximately 13 months. The primary objectives of this study are: 1) to assess the safety and reactogenicity following sequential or simultaneous IM administration of 2 doses of AS03-adjuvanted 2017 H7N9 IIV and one dose of seasonal influenza vaccine (IIV4); 2) to assess the serum HAI and Neut antibody responses against A/H7N9 at approximately 21 days following receipt of two doses of AS03-adjuvanted 2017 H7N9 IIV administered IM approximately 21 days apart; 3) to assess the serum HAI and Neut antibody responses against the seasonal influenza strains at approximately 21 days following receipt of IIV4. The secondary objectives are: 1) to assess unsolicited non-SAEs following sequential or simultaneous IM administration of AS03-adjuvanted 2017 H7N9 IIV and seasonal influenza vaccine (IIV4); 2) to assess MAAEs, including NOCMCs and PIMMCs, following sequential or simultaneous IM administration of AS03-adjuvanted 2017 H7N9 IIV and IIV4; 3) to assess the HAI and Neut antibody responses at 21 days following receipt of 1 dose of AS03-adjuvanted 2017 H7N9 IIV.

Arms: arm 1: 3.75 mcg HA per 0.5 mL dose of H7N9 vaccine in PBS diluent + GSK AS03 adjuvant and 0.5 ml dose of IIV4 vaccine, both administered intramuscularly within 15 minutes on day 1, and 3.75 mcg HA per 0.5 mL dose of H7N9 vaccine in PBS diluent + GSK AS03 adjuvant intramuscularly on day 22, n=60 arm 2: 0.5 ml dose of IIV4 vaccine intramuscularly on day 1 and 3.75 mcg HA per 0.5 ml dose of H7N9 vaccine in PBS diluent + GSK AS03 adjuvant intramuscularly on day 22 and day 43, n=60 arm 3: 0.5 ml dose of IIV4 vaccine intramuscularly on day 1, n=30
Interventions: intervention 1: AS03 intervention 2: Inactivated influenza H7N9 vaccine intervention 3: Influenza Virus Quadrivalent Inactivated Vaccine intervention 4: Phosphate Buffered Saline (PBS) diluent
Intervention descriptions: intervention 1: AS03 oil-in-water emulsion adjuvant. intervention 2: Monovalent 2017 H7N9 inactivated influenza vaccine intervention 3: A seasonal quadrivalent inactivated influenza vaccine (IIV4), prepared from influenza viruses propagated in embryonated chicken eggs, protecting against 2 influenza A subtypes (H1N1 and H3N2) and 2 influenza B subtypes (B Yamata lineage and B Victoria lineage). intervention 4: Diluent for Adjuvanted 2017 Monovalent Inactivated Influenza A/H7N9 vaccine (2017 H7N9IIV)

Protocol documents:
Prot_000.pdf: 
A Phase II Study in Healthy Adults (19-64 Years of Age) to Assess the Safety, 
Reactogenicity and Immunogenicity of Sequential or Simultaneous Intramuscular 
Administration of an AS03-adjuvanted A/H7N9 Inactivated Influenza Vaccine 
with Seasonal Influenza Vaccine 
DMID Protocol Number: 
17-0077
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: Kathleen M. Neuzil, MD, MPH 
DMID Clinical Project Manager: Tena Knudsen, RN 
DMID Medical Monitor: Shy Shorer, MD, MBA, EJD 
DMID Medical Officer: Trinka Coster, MD, MS 
DMID Scientific Lead: Chris Roberts, PhD 
Version: 5.0 
 September 18, 2018 


DMID Protocol 17-0077 
Version 5.0 
Co-Administration of AS03-adjuvanted A/H7N9 with IIV4 
September 18, 2018 
 
2 
STATEMENT OF COMPLIANCE 
This trial will be carried out in accordance with Good Clinical Practice (GCP) and as required by 
the following: 
• United States Code of Federal Regulations (CFR) 45 CFR Part 46: Protection of 
Human Subjects 
• Food and Drug Administration (FDA) Regulations, as applicable: 21 CFR Part 50 
(Protection of Human Subjects), 21 CFR Part 54 (Financial Disclosure by Clinical 
Investigators), 21 CFR Part 56 (Institutional Review Boards), 21 CFR Part 11, 
and 21 CFR Part 312 (Investigational New Drug Application), 21 CFR 812 
(Investigational Device Exemptions) 
• International Conference on Harmonisation: Good Clinical Practice (ICH E6); 62 
Federal Register 25691 (1997); and future revisions 
• Belmont Report: Ethical Principles and Guidelines for the Protection of Human 
Subjects of Research, Report of the National Commission for the Protection of 
Human Subjects of Biomedical and Behavioral Research 
• National Institutes of Health (NIH) Office of Extramural Research, Research 
Involving Human Subjects, as applicable 
• National Institute of Allergy and Infectious Diseases (NIAID) Clinical Terms of 
Award, as applicable 
• Applicable Federal, State, and Local Regulations and Guidance 


DMID Protocol 17-0077 
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Co-Administration of AS03-adjuvanted A/H7N9 with IIV4 
September 18, 2018 
 
3 
SIGNATURE PAGE 
The signature below provides the necessary assurance that this trial will be conducted according 
to all stipulations of the protocol, including all statements regarding confidentiality, and 
according to local legal and regulatory requirements and applicable US federal regulations and 
ICH E6 Good Clinical Practice (GCP) guidelines. 
 
I agree to conduct the study in compliance with GCP and applicable regulatory requirements. 
 
I agree to conduct the study in accordance with the current protocol and will not make changes to 
the protocol without obtaining the sponsor’s approval and IRB/IEC approval, except when 
necessary to protect the safety, rights, or welfare of subjects. 
 
Site Principal Investigator: 
 
Signed: 
 
 
Date: 
 
 
Name 
Title 
 
 
 


DMID Protocol 17-0077 
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4 
TABLE OF CONTENTS 
 
STATEMENT OF COMPLIANCE .................................................................................................2 
SIGNATURE PAGE ................................................................................................................................. 3 
TABLE OF CONTENTS .......................................................................................................................... 4 
LIST OF TABLES ..................................................................................................................................... 9 
LIST OF FIGURES ................................................................................................................................. 10 
LIST OF ABBREVIATIONS ................................................................................................................ 11 
PROTOCOL SUMMARY ...................................................................................................................... 14 
1 
Key Roles ........................................................................................................................................ 23 
2 
Background Information and Scientific Rationale ..................................................................... 25 
2.1 
Background Information ...........................................................................................25 
2.1.1 Public Readiness and Emergency Preparedness Act ....................................28 
2.2 
Scientific Rationale ........................................................................................................... 29 
2.3 
Potential Risks and Benefits ............................................................................................ 31 
2.3.1 Potential Risks ...................................................................................................... 31 
2.3.2 Known Potential Benefits .................................................................................... 38 
3 
Study Objectives and Outcome Measures ................................................................................... 39 
3.1 
Study Objectives ................................................................................................................ 39 
3.1.1 Primary ................................................................................................................... 39 
3.1.2 Secondary .............................................................................................................. 39 
3.1.3 Exploratory ............................................................................................................ 39 
3.2 
Study Outcome Measures ................................................................................................. 40 
3.2.1 Primary ................................................................................................................... 40 
3.2.2 Secondary .............................................................................................................. 41 
3.2.3 Exploratory ............................................................................................................ 42 
4 
Study Design ................................................................................................................................... 43 
5 
Study Enrollment and Withdrawal ............................................................................................... 45 
5.1 
Eligibility Criteria .............................................................................................................. 45 
5.1.1 Subject Inclusion Criteria .................................................................................... 45 
5.1.2 Subject Exclusion Criteria ................................................................................... 46 
5.2 
Treatment Assignment Procedures ................................................................................. 48 
5.2.1 Enrollment and Randomization Procedures ...................................................... 48 
5.2.2 Masking Procedures ............................................................................................. 49 
5.2.3 Reasons for Withdrawals and Discontinuation of Treatment ......................... 49 
5.2.4 Handling of Withdrawals and Discontinuation of Treatment ........................ 52 
5.2.5 Termination of Study ........................................................................................... 52 
6 
Study Intervention/Investigational Product................................................................................. 53 
6.1 
Study Product Description ............................................................................................... 53 


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6.1.1 Acquisition ............................................................................................................ 54 
6.1.2 Formulation, Storage, Packaging, and Labeling .............................................. 54 
6.1.3 Study Product Storage and Stability Procedures .............................................. 55 
6.2 
Dosage, Preparation, and Administration of Study Intervention/ Investigational 
Product ................................................................................................................................ 56 
6.3 
Modification of Study Intervention/Investigational Product for a Subject ................ 58 
6.4 
Accountability Procedures for the Study Intervention/ Investigational Product....... 58 
6.5 
Assessment of Subject Compliance with Study Intervention/ Investigational Product
 .............................................................................................................................................. 59 
6.6 
Concomitant Medications/Treatments ............................................................................ 59 
7 
Study Procedures and Evaluations ............................................................................................... 61 
7.1 
Clinical Evaluations .......................................................................................................... 61 
7.2 
Laboratory Evaluations ..................................................................................................... 62 
7.2.1 Clinical Laboratory Evaluations ......................................................................... 62 
7.2.2 Special Assays or Procedures ............................................................................. 63 
7.2.3 Specimen Preparation, Handling, and Shipping ............................................... 69 
7.2.3.1 Instructions for Specimen Preparation, Handling, and Storage ........69 
7.2.3.2 Specimen Shipment ................................................................................. 69 
8 
Study Schedule ............................................................................................................................... 71 
8.1 
Screening (Optional) and Enrollment Visits, All Groups ............................................ 71 
8.1.1 Visit 00, Screening Clinic Visit (Optional) (Day -28 to -1) ........................... 71 
8.1.2 Visit 01, Day 1, Enrollment (for subjects previously screened at Day -28 to -
1) and Dose 1, Clinic Visit .................................................................................. 72 
8.1.3 Visit 01, Day 1, Enrollment/Baseline (for subjects not previously screened 
at Day -28 to -1) and Dose 1, Clinic Visit ......................................................... 74 
8.2 
Follow-up Visits, Group 1 ................................................................................................ 76 
8.2.1 Visit 02, Day 4, Memory Aid Review, Phone Call ......................................... 76 
8.2.2 Visit 03, Day 8, Clinic Visit ................................................................................ 76 
8.2.3 Visit 04, Day 22, Dose 2, Clinic Visit ............................................................... 77 
8.2.4 Visit 05, Day 25, Memory Aid Review, Phone Call ....................................... 79 
8.2.5 Visit 06, Day 29, Clinic Visit ............................................................................. 79 
8.2.6 Visit 07, Day 43, Safety Follow-up Clinic Visit .............................................. 80 
8.2.7 Visit 08, Day 64, Safety Follow-up, Clinic Visit ............................................. 81 
8.2.8 Visit 09, Day 181, Safety Follow-up, Clinic Visit ........................................... 81 
8.2.9 Visit 10, Day 202, Safety Follow-up, Clinic Visit ........................................... 82 
8.2.10 Visit 11, Day 387, Safety Follow-up, Phone Call ............................................ 83 
8.3 
Follow-up Visits, Group 2 ................................................................................................ 83 
8.3.1 Visit 02, Day 4, Memory Aid Review, Phone Call ......................................... 83 
8.3.2 Visit 03, Day 8, Clinic Visit ................................................................................ 83 
8.3.3 Visit 04, Day 22, Dose 2, Clinic Visit ............................................................... 84 


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8.3.4 Visit 05, Day 25, Memory Aid Review, Phone Call ....................................... 86 
8.3.5 Visit 06, Day 29, Clinic Visit ............................................................................. 86 
8.3.6 Visit 07, Day 43, Dose 3, Clinic Visit ............................................................... 87 
8.3.7 Visit 08, Day 46, Memory Aid Review, Phone Call ....................................... 89 
8.3.8 Visit 09, Day 50, Clinic Visit ............................................................................. 89 
8.3.9 Visit 10, Day 64, Safety Follow-up, Clinic Visit ............................................. 90 
8.3.10 Visit 11, Day 181, Safety Follow-up, Clinic Visit ........................................... 91 
8.3.11 Visit 12, Day 223, Safety Follow-up, Clinic Visit ........................................... 91 
8.3.12 Visit 13, Day 408, Safety Follow-up, Phone Call ............................................ 92 
8.4 
Follow-up Visits, Group 3 ................................................................................................ 92 
8.4.1 Visit 02, Day 4, Memory Aid Review, Phone Call ......................................... 92 
8.4.2 Visit 03, Day 8, Clinic Visit ................................................................................ 93 
8.4.3 Visit 04, Day 22, Safety Follow-up, Clinic Visit ............................................. 94 
8.4.4 Visit 05, Day 43, Safety Follow-up, Clinic Visit ............................................. 94 
8.4.5 Visit 06, Day 64, Safety Follow-up, Clinic Visit ............................................. 95 
8.4.6 Visit 07, Day 181, Safety Follow-up, Clinic Visit ........................................... 95 
8.4.7 Visit 08, Day 366, Safety Follow-up, Phone Call ............................................ 96 
8.5 
Early Termination Visit (if needed) ................................................................................ 96 
8.6 
Unscheduled Visit (if needed) ......................................................................................... 98 
9 
Assessment of Safety ................................................................................................................... 100 
9.1 
Specification of Safety Parameters ............................................................................... 100 
9.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters
 ............................................................................................................................................ 100 
9.2.1 Adverse Events ................................................................................................... 100 
9.2.2 Reactogenicity .................................................................................................... 102 
9.2.3 Additional Adverse Event Severity Grading .................................................. 104 
9.2.4 Serious Adverse Events ..................................................................................... 107 
9.2.5 Procedures to be Followed in the Event of Abnormal Laboratory Test 
Values or Abnormal Clinical Findings ............................................................ 108 
9.3 
Reporting Procedures ...................................................................................................... 109 
9.3.1 Serious Adverse Events ..................................................................................... 109 
9.3.2 Regulatory Reporting for Studies Conducted Under DMID-Sponsored IND
 ............................................................................................................................... 110 
9.3.3 Reporting of Pregnancy ..................................................................................... 110 
9.4 
Type and Duration of Follow-up of Subjects after Adverse Events ......................... 110 
9.5 
Halting Rules .................................................................................................................... 111 
9.6 
Safety Oversight .............................................................................................................. 112 
9.6.1 Independent Safety Monitor (ISM) .................................................................. 112 
9.6.2 Data and Safety Monitoring Board (DSMB) .................................................. 113 
10 
Clinical Monitoring ...................................................................................................................... 115 


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10.1 
Site Monitoring Plan ....................................................................................................... 115 
11 
Statistical Considerations ............................................................................................................ 116 
11.1 
Introduction ...................................................................................................................... 116 
11.2 
Study Hypotheses ............................................................................................................ 116 
11.3 
Study Outcome Measures ............................................................................................... 116 
11.4 
Sample Size Considerations ........................................................................................... 116 
11.4.1 Study Population ................................................................................................ 116 
11.4.2 Subject Enrollment and Follow-up .................................................................. 117 
11.4.3 Sample Size ......................................................................................................... 117 
11.5 
Planned Interim Analyses ............................................................................................... 119 
11.5.1 Interim Safety Review ....................................................................................... 120 
11.5.2 Interim Immunogenicity Review ...................................................................... 120 
11.6 
Final Analysis Plan .......................................................................................................... 121 
11.6.1 Analysis Populations .......................................................................................... 121 
11.6.2 Safety Data .......................................................................................................... 122 
11.6.3 Immunogenicity Data......................................................................................... 123 
11.6.4 Missing Values and Outliers ............................................................................. 124 
12 
Data Collection Forms and Access to Source Data/Documents ............................................ 125 
13 
Quality Control and Quality Assurance ..................................................................................... 126 
14 
Ethics/Protection of Human Subjects ........................................................................................ 127 
14.1 
Ethical Standard ............................................................................................................... 127 
14.2 
Institutional Review Board............................................................................................. 127 
14.3 
Informed Consent Process .............................................................................................. 127 
14.3.1 Informed Consent ............................................................................................... 127 
14.4 
Exclusion of Women, Minorities, and Children (Special Populations) ................... 128 
14.5 
Subject Confidentiality ................................................................................................... 129 
14.6 
Study Discontinuation ..................................................................................................... 130 
14.7 
Costs, Subject Compensation, and Research Related Injuries .................................. 131 
14.8 
Future Use of Stored Specimens ................................................................................... 131 
15 
Data Handling and Record Keeping .......................................................................................... 133 
15.1 
Data Management Responsibilities ............................................................................... 133 
15.2 
Data Capture Methods .................................................................................................... 133 
15.3 
Types of Data ................................................................................................................... 134 
15.4 
Timing/Reports ................................................................................................................ 134 
15.5 
Study Records Retention ................................................................................................ 135 
16 
Protocol Deviations ...................................................................................................................... 136 
17 
Publication Policy ......................................................................................................................... 137 
18 
Literature References ................................................................................................................... 138 
Appendices .............................................................................................................................................. 143 
APPENDIX A: SCHEDULE OF STUDY PROCEDURES AND EVALUATIONS .................. 144 


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APPENDIX B: LIST OF POTENTIALLY IMMUNE-MEDIATED MEDICAL CONDITIONS
 ......................................................................................................................................................... 154 
 
 
 


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LIST OF TABLES 
Table 1: Study Design ....................................................................................................................21 
Table 2 a 
 ....................................................................................................................................65 
Table 2 b  ....................................................................................................................................67 
Table 2 c 
 ....................................................................................................................................69 
Table 3: Power (%) to Detect Safety Events: ..............................................................................117 
Table 4: Precision of Binomial Confidence Intervals: .................................................................118 
Table 5: Objective 1 -Minimum Detectable Difference in Proportion Responders with 
80% Power (N = 50 per group).................................................................................118 
Table 6: Objective 2 - Minimum Detectable Difference in Proportion Responders with 
80% Power ................................................................................................................119 
 
 
 
 


DMID Protocol 17-0077 
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LIST OF FIGURES 
Figure 1: Schematic of Study Design ............................................................................................22 
 


DMID Protocol 17-0077 
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LIST OF ABBREVIATIONS 
A/H1N1 
Influenza A Virus of the H1N1 Subtype 
A/H2N2 
Influenza A Virus of the H2N2 Subtype 
A/H3N2 
A/H3N2v 
Influenza A Virus of the H3N2 Subtype 
Influenza A Virus of the H3N2 Variant Subtype 
A/H5N1  
A/H5N2 
A/H5N3 
A/H5N6 
Influenza A Virus of the H5N1 Subtype 
Influenza A Virus of the H5N2 Subtype 
Influenza A Virus of the H5N3 Subtype 
Influenza A Virus of the H5N6 Subtype 
A/H7N7 
Influenza A Virus of the H7N7 Subtype 
A/H7N9 
Influenza A Virus of the H7N9 Subtype 
AS03 
Adjuvant System 03 
AdvantageEDCSM 
Electronic Data Capture System 
AE 
Adverse Event/Adverse Experience 
AESI 
Adverse Event of Special Interest 
ALT 
Alanine Aminotransferase 
ANCA 
Anti-Neutrophil Cytoplasmic Antibody 
BARDA 
Biomedical Advanced Research and Development Authority 
BLA 
Biologics License Applications 
BMI 
Body Mass Index 
BPM 
Beats Per Minute 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CHMP 
Committee for Medicinal Products for Human Use 
CI 
CMS 
Confidence Interval 
Clinical Materials Services 
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 
DSMB 
Data and Safety Monitoring Board 
eCRF 
Electronic Case Report Form 
ESR 
Erythrocyte Sedimentation Rate 


DMID Protocol 17-0077 
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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 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
 International Conference on Harmonisation 
ICMJE 
International Committee of Medical Journal Editors 
IgG 
Immunoglobulin G 
IIV 
Inactivated Influenza Vaccine 
IIV3 
Trivalent Inactivated Influenza Vaccine 
IIV4 
Quadrivalent Inactivated Influenza Vaccine 
IM 
Intramuscular 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
IU/L 
International Unit(s) per Liter 
mcg  
Microgram(s) 
µL 
Microliter(s) 
MAAEs 
Medically-Attended Adverse Events 
MedDRA 
Medical Dictionary for Regulatory Activities 
MF59 
 MF59C.1 Adjuvant 
mg/dL 
Milligram(s) per Deciliter 
mITT 
Modified Intent-to-Treat 
mL 
Milliliter(s) 
mm 
Millimeter(s) 
mmHg 
Millimeters of Mercury 
MOP 
Manual of Procedures 


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N 
Number of Subjects 
NA 
Neuraminidase 
Neut 
Neutralizing or Neutralization 
NI  
Neuraminidase Inhibiting 
NIAID 
National Institute of Allergy and Infectious Diseases, DHHS 
NIH 
National Institutes of Health 
NSAIDs 
Non-Steroidal Anti-Inflammatory Drugs 
NOCMCs 
New-Onset Chronic Medical Conditions 
OER 
Office of Extramural Research 
OHRP 
Office for Human Research Protections 
PBS 
Phosphate Buffered Saline 
pH1N1 
2009 H1N1 Influenza 
PHI 
Personal Health Information 
PIMMCs 
Potentially Immune-Mediated Medical Conditions 
PLT 
Platelets 
PP 
Per Protocol 
PREP Act 
Public Readiness and Emergency Preparedness Act 
PRN 
As Needed 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SAP 
Statistical Analysis Plan 
SDCC 
Statistical and Data Coordinating Center 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
T. Bili 
Total Bilirubin 
TBD 
To Be Determined 
US 
United States 
V 
Visit(s) 
VTEU 
Vaccine and Treatment Evaluation Unit 
WBC 
White Blood Cells 
WHO 
World Health Organization 


DMID Protocol 17-0077 
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Co-Administration of AS03-adjuvanted A/H7N9 with IIV4 
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PROTOCOL SUMMARY 
Title: 
A Phase II Study in Healthy Adults (19-64 Years of Age) to Assess the 
Safety, Reactogenicity and Immunogenicity of Sequential or 
Simultaneous Intramuscular Administration of an AS03-adjuvanted 
A/H7N9 Inactivated Influenza Vaccine with Seasonal Influenza Vaccine 
 
Phase: 
II 
Population: 
Approximately 150 individuals 19-64 years old, who have no history of 
influenza A/H7N9 infection or prior receipt of an influenza virus H7 
subtype vaccine. 
Number of Sites: 
Up to 4 Vaccine and Treatment Evaluation Unit (VTEU) sites 
Study Duration: 
Approximately sixteen (16) months 
Subject Participation 
Duration: 
Approximately thirteen (13) months 
Estimated Time to Complete 
Enrollment: 
Approximately 12 weeks 
Description of Agent: 
Two doses delivered intramuscularly (IM) approximately 21 days apart 
of an AS03-adjuvanted 2017 H7N9 inactivated influenza vaccine (IIV) 
(3.75 mcg hemagglutinin [HA] from A/Hong Kong/125/2017 H7N9 
vaccine per dose) administered with a licensed seasonal influenza 
vaccine (15 mcg HA per strain per dose, quadrivalent IIV [IIV4]) given 
simultaneously with the first AS03-adjuvanted 2017 A/H7N9 IIV dose 
or sequentially at approximately 21 days prior to the first AS03-
adjuvanted 2017 A/H7N9 IIV dose.  One arm receiving only IIV4 is 
included as a comparator. All doses are to be given un-blinded following 
randomization. 
Study Objectives: 
 
Primary: 
Safety: 
• 
To assess the safety and reactogenicity following sequential or 
simultaneous IM administration of 2 doses of AS03-adjuvanted 
2017 H7N9 IIV and one dose of seasonal influenza vaccine 
(IIV4).  
Immunogenicity: 


DMID Protocol 17-0077 
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Co-Administration of AS03-adjuvanted A/H7N9 with IIV4 
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• 
To assess the serum hemagglutination inhibition (HAI) and 
neutralizing (Neut) antibody responses against A/H7N9 at 
approximately 21 days following receipt of two doses of AS03-
adjuvanted 2017 H7N9 IIV administered IM approximately 21 
days apart. 
• 
To assess the serum HAI and Neut antibody responses against 
the seasonal influenza strains at approximately 21 days 
following receipt of IIV4. 
 
Secondary: 
Safety: 
• 
To assess unsolicited non-serious adverse events (AEs), 
following sequential or simultaneous IM administration of 
AS03-adjuvanted 2017 H7N9 IIV and seasonal influenza 
vaccine (IIV4).  
• 
To assess medically-attended adverse events (MAAEs), 
including new-onset chronic medical conditions (NOCMCs) and 
potentially immune-mediated medical conditions (PIMMCs), 
following sequential or simultaneous IM administration of AS03 
adjuvanted 2017 H7N9 IIV and IIV4. 
Immunogenicity: 
• 
To assess the HAI and Neut antibody responses at 21 days 
following receipt of 1 dose of AS03-adjuvanted 2017 H7N9 IIV. 
 
Exploratory: 
Immunogenicity: 
• 
To assess the effects of age, sex, body mass index (BMI), and 
receipt of prior year(s) seasonal influenza vaccine(s) on serum 
HAI antibody responses following receipt of two doses of 
AS03-adjuvanted 2017 H7N9 IIV.  
• 
To assess the durability of the antibody response to the 2017 
H7N9 study vaccine strain and the IIV4 strains at approximately 
180 days following the second dose of AS03-adjuvanted 2017 
H7N9 IIV vaccine. 
• 
To assess the neuraminidase (NA) content of the 2017 H7N9 
IIV and the licensed seasonal IIV4 and determine the serum 
antibody responses to NA following receipt of 2017 H7N9 IIV 
and licensed seasonal IIV4. 
 


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Study Outcome Measures: 
 
Primary: 
Safety: 
• 
Occurrence of all serious adverse events (SAEs) following the 
first study vaccination through approximately 12 months after 
the last study vaccination. 
• 
Occurrence of study vaccine-related SAEs following the first 
study vaccination through approximately 12 months after the 
last study vaccination. 
• 
Occurrence of solicited injection site and systemic AEs 
following each study vaccination through 7 days after each 
study vaccination.  
• 
Occurrence of clinical safety laboratory AEs following each 
study vaccination through approximately 7 days after each study 
vaccination. 
Immunogenicity: 
• 
For HAI and Neut antibodies, percentage of subjects achieving 
seroconversion against the 2017 H7N9 study vaccine strain 
(defined as either a pre-vaccination titer <1:10 and a post-
vaccination titer ≥1:40 or a pre-vaccination titer ≥1:10 and a 
minimum four-fold rise in post-vaccination antibody titer) at 
approximately 21 days after 2 doses of AS03-adjuvanted 2017 
H7N9 IIV (Group 1– Day 43; Group 2 – Day 64; Group 3 – 
N/A). 
• 
For HAI and Neut antibodies, percentage of subjects achieving 
seroconversion against each of the study IIV4 strains at 
approximately 21 days after receipt of study IIV4 (Groups 1, 2 
and 3 – Day 22).  
• 
For HAI and Neut antibodies, percentage of subjects with an 
antibody titer of ≥1:40 against the influenza 2017 H7N9 study 
vaccine strain at approximately 21 days following receipt of 2 
doses of AS03-adjuvanted 2017 H7N9 IIV (Group 1– Day 43; 
Group 2 – Day 64; Group 3 – N/A). 
• 
For HAI and Neut antibodies, percentage of subjects with an 
antibody titer of ≥1:40 against each of the study IIV4 strains at 
approximately 21 days after receipt of study IIV4 (Groups 1, 2 
and 3 – Day 22).  
• 
Geometric Mean Titers (GMTs) of serum HAI and Neut 
antibodies against the 2017 H7N9 IIV strain at approximately 21 


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days following receipt of 2 doses of AS03-adjuvanted 2017 
H7N9 IIV (Group 1– Day 43; Group 2 – Day 64; Group 3 – 
N/A).  
• 
GMTs of serum HAI and Neut antibodies against each of the 
2017 IIV4 strains at approximately 21 days after receipt of IIV4 
(Groups 1, 2, and 3 – Day 22). 
 
Secondary: 
Safety: 
• 
Occurrence of study vaccine-related unsolicited non-serious AEs 
following each study vaccination through approximately 21 days 
after each study vaccination. 
• 
Occurrence of all unsolicited non-serious AEs following each 
study vaccination through approximately 21 days after each 
study vaccination.  
• 
Occurrence of MAAEs, including NOCMCs and PIMMCs, 
following the first study vaccination through approximately 12 
months after the last study vaccination. 
Immunogenicity: 
• 
For HAI and Neut antibodies, percentage of subjects achieving 
seroconversion against the 2017 H7N9 vaccine strain at 
approximately 21 days after receipt of 1 dose of AS03-
adjuvanted 2017 H7N9 IIV (Group 1– Day 22; Group 2 – Day 
43; Group 3 – N/A). 
• 
For HAI and Neut antibodies, percentage of subjects achieving 
serum HAI and Neut antibody titers ≥1:40 against the influenza 
2017 H7N9 vaccine strain at baseline and approximately 21 
days after receipt of 1 dose of AS03-adjuvanted 2017 H7N9 IIV 
(Group 1–Day 1 (baseline) and Day 22; Group 2 –Day 22 
(baseline), and Day 43; Group 3 – N/A). 
• 
GMTs of serum HAI and Neut antibodies against the influenza 
2017 H7N9 vaccine virus at baseline and at approximately 21 
days after receipt of 1 dose of AS03-adjuvanted 2017 H7N9 IIV 
(Group 1–Day 1 (baseline) and Day 22; Group 2 –Day 22 
(baseline), and Day 43; Group 3 – N/A). 
Exploratory: 


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Immunogenicity: was manufactured using 
• 
For HAI and Neut antibodies, percentage of subjects achieving 
seroconversion, percentage with titer ≥1:40 and the GMTs 
against the 2017 H7N9 study vaccine strain approximately 21 
and 180 days after 2 doses of adjuvanted 2017 H7N9 IIV, 
stratified by age, sex, BMI, and prior receipt of seasonal 
influenza vaccine(s) for Groups 1 and 2. 
• 
For HAI and Neut antibodies, percentage of subjects achieving 
seroconversion, percentage with a titer ≥1:40 and the GMTs 
against the IIV4 vaccine strains approximately 21 and 180 days 
after receipt of IIV4, stratified by age, sex, BMI, and prior 
receipt of seasonal influenza vaccine(s). 
• 
For HAI and Neut antibodies, percentage of subjects achieving 
seroconversion, percentage with titer ≥1:40, and GMTs against 
the 2017 H7N9 study vaccine strain at approximately 180 days 
after 2 doses of adjuvanted 2017 H7N9 IIV for Groups 1 and 2. 
• 
Percentage of subjects with detectable levels of serum N1, N2 
and N9 NA-specific antibody elicited by 2017 H7N9 and 
seasonal IIV4 vaccination, and the correlation of the NA content 
of 2017 H7N9 IIV and seasonal IIV4 with the elicited NA-
specific antibody responses at baseline and approximately 21 
and 180 days after 2 doses of adjuvanted 2017 H7N9 IIV for 
Groups 1 and 2, and approximately 21 and 180 days after receipt 
of the seasonal IIV4 vaccine for all Groups. 
 
Description of Study Design: 
This is a randomized, un-blinded, Phase II study in males and non-
pregnant females, who are in good health, 19 to 64 years of age. This 
clinical trial is designed to assess the safety, reactogenicity, and 
immunogenicity of a pre-pandemic AS03 (GlaxoSmithKline Biologicals 
[GSK]) adjuvanted 2017 monovalent inactivated influenza A/H7N9 
vaccine (2017 H7N9 IIV) manufactured by Sanofi Pasteur (3.75 mcg of 
HA per dose), with Phosphate Buffered Saline (PBS) diluent, when two 
doses are administered 21 days apart either sequentially or 
simultaneously (within 15 minutes) with licensed seasonal influenza 
vaccine.
 
 
IIV4 will be provided through the Division of Microbiology and 
Infectious Diseases (DMID) DMID Clinical Materials Services 
Contract (CMS), Fisher BioServices. 


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Subjects will be randomized into one of three treatment groups as shown 
in Table 1. Group 1 will receive two doses of AS03-adjuvanted 2017 
H7N9 IIV, each dose administered IM approximately 21 days apart, and 
one dose of licensed seasonal IIV4 will be administered IM 
simultaneously (within 15 minutes) in opposite arms with the first dose 
of AS03 adjuvanted 2017 H7N9 IIV. Group 1 is the only Group, and 
only on study Day 1, that subjects will receive two vaccines 
administered IM simultaneously.  Group 2 will receive one dose of 
IIV4 approximately 21 days prior to the IM administration of two doses 
of AS03-adjuvanted 2017 H7N9 IIV; each dose of AS03-adjuvanted 
2017 H7N9 IIV will be given approximately 21 days apart. In Groups 1 
and 2, the second dose of adjuvanted 2017 H7N9 IIV may be 
administered in the subject’s preferred arm. If the subject has no 
preference, the second dose of adjuvanted 2017 H7N9 IIV may be given 
in either arm as long as there is no hindrance of the reactogenicity 
assessment. Group 3 will receive one dose IM of IIV4 as an un-blinded 
comparator in the subject’s preferred arm. 
Subjects who are in good health and meet all eligibility criteria 
(including an erythrocyte sedimentation rate [ESR], urine or serum 
pregnancy test, history and physical exam) within 28 days prior to the 
first vaccination or on the day of, but prior to, the first vaccination will 
be eligible for randomization as stated above. Baseline clinical safety 
laboratories will be drawn prior to the first vaccine dose and will not be 
used to screen subjects for eligibility. 
Reactogenicity will be measured by the occurrence of solicited injection 
site and systemic reactions from the time of each study vaccination 
through 7 days after each study vaccination. Unsolicited non-serious 
AEs will be collected from the time of each study vaccination through 
approximately 21 days after each study vaccination. SAEs and MAAEs, 
including NOCMCs and PIMMCs, will be collected from the time of the 
first study vaccination through approximately 12 months after the last 
study vaccination. Clinical laboratory evaluations for safety will be 
performed on venous blood collected prior to each study vaccination and 
approximately 7 days after each study vaccination. 
Immunogenicity testing will include performing HAI and Neut antibody 
assays against the 2017 H7N9 vaccine virus on serum samples collected 
for Group 1 on Days 1 (baseline), 22, and 43, and at approximately 180 
days post second 2017 H7N9 IIV dose (Day 202), and for Group 2 on 
Days 22 (baseline), 43, and 64, and at approximately 180 days post 
second 2017 H7N9 IIV dose (Day 223). Serological antibody assays will 


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be performed against the vaccine viruses in IIV4 from serum samples 
collected at baseline (Day 1) and approximately 21 and 180 days 
following receipt of IIV4 (Groups 1, 2, and 3).   
Novel methods for identifying and assessing alternative correlates of 
protection against influenza infection are needed.  To assess the NA 
specific antibody response to vaccination, it is first necessary to 
determine the NA content of inactivated influenza vaccine; this assay is 
under development.  If successful, the NA content in a dosage-specific 
manner can be correlated to the N9 NA-specific antibody responses 
elicited by the 2017 H7N9 IIV. 
Subjects will be ineligible to participate in this trial if they have received 
the licensed 2017-2018 licensed seasonal IIV (IIV3 or IIV4, including 
high dose vaccine for the elderly) any time prior to enrollment; IIV4 will 
be provided at the first study vaccination to all participants in the study. 
 
 


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Table 1: Study Design 
 
Day 1 
Dose 1 
Approximately Day 22 
Dose 2 
Approximately Day 43 
Dose 3 
Group 1 
(Age 19-64) 
 n=60 
Dose 1 (First and Second 
Study Vaccinations):  
Sanofi Pasteur H7N9 
vaccine 3.75 mcg/ PBS 
diluent, plus GSK AS03 
adjuvant 
+ IIV4 
Dose 2 (Third Study 
Vaccination): 
Sanofi Pasteur H7N9 
vaccine 3.75 mcg/ PBS 
diluent, plus GSK AS03 
adjuvant 
 
N/A  
Group 2 
(Age 19-64) 
 n=60 
Dose 1 (First Study 
Vaccination): 
IIV4 
 
Dose 2 (Second Study 
Vaccination): 
Sanofi Pasteur H7N9 
vaccine 3.75 mcg/ PBS 
diluent, plus GSK AS03 
adjuvant 
 
Dose 3 (Third Study 
Vaccination): 
Sanofi Pasteur H7N9 
vaccine 3.75 mcg/ PBS 
diluent, plus GSK AS03 
adjuvant 
 
Group 3 
(Age 19-64) 
 n=30 
Dose 1 (First Study 
Vaccination): 
IIV4  
 
N/A 
N/A 
Total 
Enrollment, 
n = ~150 
Blood for HAI/Neut assays for 2017 H7N9 IIV will be collected:  
• 
for Group 1 on Days 1 (baseline), 22, and 43, and at approximately 180 
days post second adjuvanted 2017 H7N9 IIV dose (Day 202) 
• 
for Group 2, on Days 22 (baseline), 43, and 64, and at approximately  
180 days post second 2017 H7N9 IIV dose (Day 223). 
 
Serological antibody assays will also be performed against the vaccine viruses in 
IIV4 from serum samples collected at baseline (Day 1) and approximately 21 and 
180 days following receipt of IIV4 (Groups 1, 2 and 3). 
 
Safety Lab Timepoints: 
Group 1: 4 timepoints per subject (Days 1, 8, 22, and 29)  
Group 2: 6 timepoints per subject (Days 1, 8, 22, 29, 43, and 50) 
Group 3: 2 timepoints per subject (Days 1 and 8) 
and Early Termination and /or Unscheduled Visits 
 


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Figure 1: Schematic of Study Design
 
 
 
Planned Enrollment: Total N=~150 Subjects 
 
The study is planned to enroll a minimum of 150 subjects with a target of  
60 in Groups 1and 2, and 30 in Group 3. 
 
Administer Study Vaccine per Subject Treatment Assignments on 
Day 1, and approximately Day 22 and Day 43  
Assessment of Final 
Outcome Measures 
Consent 
 
Assess Eligibility 
19-64 Years Old 
(N = ~150) 
Randomize 2:2:1 
Clinical, Safety, Reactogenicity, and 
Immunogenicity Assessments 


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1 
KEY ROLES 
Lead Principal Investigator: 
 
Kathleen M. Neuzil, MD, MPH 
Professor of Medicine and Pediatrics 
Director, Center for Vaccine Development 
University of Maryland School of Medicine 
 
Co-Investigators: 
Paul W. Spearman, MD (CCHMC) 
Cincinnati Children's Hospital Medical Center 
 
C. Buddy Creech, MD, MPH (Vanderbilt) 
Associate Professor of Pediatrics, Division of Pediatric 
Infectious Diseases 
Director, Vanderbilt Vaccine Research Program 
 
Paul Goepfert, MD (UAB) 
Professor of Medicine 
Director, Alabama Vaccine Research Clinic 
 
 
DMID Clinical Project Manager: 
Tena Knudsen, RN 
Division of Microbiology and Infectious Diseases 
NIAID, NIH 
5601 Fishers Lane, Room 8E36,  
Bethesda, MD 20892-9825 
Work: 240-627-3290 
Email: knudsent@niaid.nih.gov 
 
DMID Medical Monitor: 
Shy Shorer, MD, MBA, RAC 
Division of Microbiology and Infectious Diseases 
NIAID, NIH 
5601 Fishers Lane, Room 7E50 
Rockville, MD 20892-9825 
Phone: 240-627-3371 
Email: shorers@niaid.nih.gov 
 
DMID Medical Officer: 
 
Trinka Coster, MD, MS 
Medical Officer, Respiratory Disease Branch 
Division of Microbiology and Infectious Diseases 
NIAID, NIH  
5601 Fishers Lane, Room 8E25, MSC 9826 


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Bethesda, MD 20852  
Work: 301 538-2963 
Email: trinka.coster@nih.gov 
 
DMID Scientific Lead: 
 
Chris Roberts, Ph.D. 
Division of Microbiology and Infectious Diseases 
NIAID/NIH/DHHS 
 
Safety and Pharmacovigilance 
Contractor: 
 
DMID Pharmacovigilance Group 
Clinical Research Operations and Management Support 
(CROMS) 
6500 Rock Spring Dr., Suite 650 
Bethesda, MD 20814 
SAE Hot Line: 1-800-537-9979 (US) 
SAE Fax: 800-275-7619 (US) 
SAE Email: PVG@dmidcroms.com 
 
 
Statistical and Data Coordinating 
Center: 
The Emmes Corporation 
401 N. Washington St., Suite 700 
Rockville, MD 20850 
Phone: 301-251-1161 
Email: flutrials@emmes.com 
 
Study Agent Repository: 
Fisher BioServices 
c/o DMID Clinical Materials Services (CMS) 
Contract 
20439 Seneca Meadows Parkway 
Germantown, MD 20876 
Phone: 240-477-1350 
Fax: 240-477-1360 
Email: DMID.CMS@ThermoFisher.com 
 
HAI and Neut Antibody Assays 
Laboratory: 
 
 
NA Content Assays and NA 
Antibody Assays Laboratory: 
 
Southern Research 
2000 9th Avenue South 
Birmingham, AL 35205 
 
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, 
H3N2v, H7N7, H9N2, 2009 H1N1, and most recently H5N6 and H7N9, underscores the need 
for focused efforts to prepare for the next influenza pandemic [1-6]. Four pandemics occurred 
during the last century. It was estimated that during the 1918 influenza A/H1N1 pandemic as 
many as 40 million deaths occurred worldwide [7]. Excess mortality, high morbidity, and social 
disruption were all noted during the 1957 influenza A/H2N2 and the 1968 influenza A/H3N2 
pandemics [8]. In April 2009, a novel influenza virus (2009 A/H1N1) originated in pigs and 
spread to humans around the world becoming the first pandemic of this century. In each of these 
influenza pandemics, human populations lacked significant levels of pre-existing immunity to a 
highly transmissible form of the virus enabling it to spread rapidly. Thus, each emergence of a 
new strain of influenza virus in the human population has the potential to result in a global public 
health emergency. 
A major cornerstone of pandemic preparedness is the capacity to rapidly produce and deliver 
sufficient quantities of safe and effective strain-specific pandemic influenza vaccines. The threat 
of pandemic influenza in 1976 (swine influenza) and again in 1977 (Russian influenza) resulted 
in IIV development programs that provided important insights into variables influencing the 
immune responses to immunization [9, 10]. Vaccine- associated factors potentially affecting the 
immunogenicity of IIVs that were noted during the 1976 experience and have been refined in 
subsequent years include the amount of viral 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 NA, the major surface glycoproteins on 
influenza viruses, play a key role in protective immunity to influenza virus infection [11]. Since 
protection against infection with seasonal influenza virus strains has been shown to correlate 
with both serum HAI and Neut antibody levels, their measurements are used routinely to assess 
the immunogenicity of both seasonal and pandemic IIVs. Recent data also supports an important 
role for neuraminidase inhibiting (NI) antibodies in protection against disease [12]. In a recent 
human influenza challenge study, serum NI antibody levels were also identified as an 
independent correlate of protection against influenza illness [13].  In the current study, we plan 


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to assess the NA content of 2017 H7N9 IIV and determine the correlation of NA content at 
different vaccine dosages with the elicited humoral antibody responses to the NA. 
Several approaches have been used to increase the immunogenicity of IIVs. Standard-dose 
inactivated seasonal influenza vaccines contain 7.5 mcg of HA antigen per vaccine strain (for 
children aged <36 months) or 15 mcg of HA antigen per vaccine strain (for persons aged ≥36 
months). Clinical studies evaluating increased HA-containing influenza vaccines performed over 
the past 35 years have shown dose-related increases in serum and mucosal antibody responses 
[14-22]. Higher HA dosage vaccines can lead to enhanced antibody responses in the elderly [23]. 
In 2009, a high-dose IIV containing 4 times the standard HA antigen per seasonal vaccine strain 
was approved in the 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, and 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 [24, 25]). Due to the poor immunogenicity of H5 and H7 
vaccines, the inclusion of adjuvants was evaluated to assess their ability to boost anti-viral serum 
immunoglobulin G (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 [26-28]. In contrast, the use of oil-in-water emulsion 
adjuvants, most notably proprietary adjuvants AS03 and MF59 produced by GSK and Seqirus, 
respectively, has resulted in increased antibody responses to IIVs containing novel HAs in 
numerous clinical trials [29-33]. In an early study, dosage levels ranging from 3.75 to 30 mcg of 
A/H5N1 antigen administered with or without AS03 resulted in significant increases in antibody 
GMTs in groups who received the adjuvanted formulations [31]. These GMTs met the 
Committee for Medicinal Products for Human Use (CHMP) criterion for seroconversion rate 
(>40%) after a single dose with adjuvant. Following the second vaccine dose, all adjuvanted 
formulations complied with both CHMP and US Food and Drug Administration (FDA) criteria 
for seroconversion and seroprotection rates, whereas from the non-adjuvanted groups only the 30 
mcg formulation met the CHMP criterion for seroconversion [31]. GSK received approval for 
the registration of a pre-pandemic AS03-adjuvanted, monovalent inactivated A/H5N1 virus 
vaccine by European regulatory authorities in 2008 and FDA approval of their Biologics License 
Applications (BLA) for 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 
2009 A/H1N1 virus vaccine (Pandemrix™) and Novartis’ egg-derived MF59-adjuvanted, 
monovalent inactivated 2009 A/H1N1 virus vaccine (FOCETRIATM). These adjuvanted 


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


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


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An individual who suffers a serious physical injury or death from administration and use of the 
2017 H7N9 IIV with or without adjuvant may request benefits from CICP. A serious physical 
injury means an injury that is life threatening, results in, or requires, medical or surgical 
intervention to prevent permanent impairment of a body function, or permanent damage to body 
structure. The CICP is the payer of last resort. This means that it only covers expenses or 
provides benefits that other third-party payers, such as health insurance, the Department of 
Veterans Affairs, or Workers’ Compensation programs don’t have an obligation to pay. 
If no funds have been appropriated to the compensation program, the Secretary of HRSA does 
not make a final determination on the individual’s request within 240 days, or if the individual 
decides not to accept the compensation, the injured individual or his representative may pursue a 
tort claim in the US District Court for the District of Columbia, but only if the claim involves 
willful misconduct, is pled with particularity required under the PREP Act, verified, and 
accompanied by an affidavit by a physician who did not treat the individual and certified medical 
records. Any award is reduced by any public or private insurance or worker’s compensation 
available to the injured individual. Awards for non-economic damages, such as pain, suffering, 
physical impairment, mental anguish, and loss of consortium are also limited. If the individual 
accepts compensation, or if there is no willful misconduct, then the individual does not have a 
tort claim that can be filed in a United States Federal or a State court. 
2.2 
Scientific Rationale 
As part of the US Government’s past pandemic preparedness efforts, Sanofi Pasteur under 
contract to the Biomedical Advanced Research and Development Authority (BARDA)/DHHS, 
produced several novel pre-pandemic vaccines that were evaluated by NIAID’s VTEU sites to 
assess their safety, reactogenicity, and immunogenicity when mixed prior to administration with 
either AS03 or MF59 oil-in-water adjuvants manufactured by GSK and Novartis (now Seqirus), 
respectively. In general, these trials have demonstrated that adjuvant use results in a significant 
dose-sparing effect. NIAID is currently conducting similar “mix and match” clinical trials using 
an H5N8 vaccine antigen produced by Seqirus and mixed with either AS03 or MF59 adjuvants 
(NCT03014310, NCT02624219). 
The large number of human infections starting with the “fifth wave” of H7N9 outbreaks in late 
2016, has raised the pandemic risk assessment of influenza A/H7N9 viruses circulating in China. 
The Yangtze River Delta lineage, a distinct H7N9 viral lineage, has now emerged and has been 
associated with many of the cases in the fifth epidemic wave. This has also resulted in a broader 
geographic spread of infected birds and human cases within China than previously reported. 
Further, several H7N9 viruses in the Yangtze River Delta lineage have recently acquired genetic 
changes characteristic of HPAI viruses and have now shown an increased ability to infect and 
kill poultry [54, 58]. To date, no cases of H7N9 from the new lineage have been identified in 


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birds or people infected outside of China; however, a few cases have been identified in Hong 
Kong and Taiwan in infected travelers returning from China. Importantly, antigenic analysis of 
the fifth wave H7N9 viruses and serology studies indicate that the stockpiled H7N9 vaccine 
manufactured several years ago does not induce protective HAI or Neut antibodies against the 
Yangtze River Delta lineage. Hence, there is broad consensus across HHS and interagency 
leadership that a new vaccine should be developed that would be effective against the currently 
predominating H7N9 viruses.  
The potential for a negative effect of prior seasonal vaccination on vaccine effectiveness and 
immunogenicity has been debated for decades [59, 60].  In recent years, several observational 
studies have reported that the response to and effectiveness of influenza vaccine during any 
given season may be modified by receipt of seasonal influenza vaccine in prior seasons [61-63].     
Likewise, several evaluations of H5N1 and 2009 H1N1 vaccines suggest that prior receipt of 
seasonal vaccine is associated with a lower response to H5N1 or 2009 H1N1 vaccines, 
respectively [64-67]. Similar immunological interference has been reported in individuals who 
received seasonal IIV3 in the weeks to months prior to H1N1 and H5N1 vaccines, whereas other 
studies failed to identify significant differences or observed improved responses [67-69].    
 
Overall, the effects of prior vaccination have not been observed consistently across all studies 
and seasons, and likely differ by timing of vaccine administration, influenza virus type or 
subtype, and presence and type of adjuvant used.  In regards to H7N9 vaccines, as reported by 
Jackson et al., generally higher GMTs and proportion with an HAI titer of 40 or higher at 21 
days after dose 2 were observed in the group that did not receive seasonal influenza vaccine.  In 
a logistic regression model, older age and prior receipt of seasonal influenza vaccine were 
independently associated with a lower likelihood of achieving an HAI titer of 40 or higher after 
dose 2 [47].  In the Jackson et al. study, the receipt of seasonal vaccines occurred before the start 
of the trial, as reported by the participants.  Data from randomized control trials of seasonal 
vaccines given concomitantly or sequentially with H7N9 vaccines are not available. 
The goal of this clinical trial is to assess the safety, reactogenicity and immunogenicity of two 
doses of AS03-adjuvanted 2017 H7N9 IIV administered sequentially or simultaneous with 
seasonal influenza vaccine and to assess potential interference with the immunogenicity of either 
vaccine. The public health goal would be to maximize protection to the seasonal strains and 
H7N9 strain in the target population while ensuring acceptable tolerability and safety.  While the 
prior seasonal influenza vaccine history of the target population will vary substantially and 
cannot be readily altered, it is important to understand the effects of simultaneous versus 
sequential delivery of H7N9 strains with currently available seasonal influenza vaccines to 
inform vaccination programs.  This study will provide important information on two scenarios 1) 
seasonal influenza vaccine given with the first dose of H7N9 and 2) seasonal influenza vaccine 
given prior to H7N9 vaccine. 


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Another goal of this study is to assess, in at least a subset of samples, if serum IgG elicited by the 
2017 H7N9 IIV recognize antigenically drifted variants of influenza A/H7 viruses. Since 
antibodies targeting the NA may represent an independent correlate of protection against 
influenza infection [11-13], we plan to assess the NA content of the 2017 H7N9 vaccine and 
determine if there is a dose-specific correlation of NA content with elicited humoral antibody 
responses to the N9 NA. 
Based on previously conducted studies with a 2013 H7N9 IIV manufactured by Sanofi Pasteur 
administered with AS03, we anticipate that two doses of the 2017 H7N9 IIV administered IM 
with AS03 adjuvant approximately 21 days apart will be well-tolerated. 
2.3 
Potential Risks and Benefits 
2.3.1 
Potential Risks 
The potential risks of participating in this trial are those associated with having blood drawn, the 
IM injection and possible reactions to the monovalent inactivated influenza H7N9 vaccine plus 
PBS diluent and/or AS03 adjuvant, and breach of confidentiality. 
Drawing blood may cause transient discomfort and fainting. Fainting is usually transient and 
managed by having the subject lie down and elevate his/her legs. Bruising at the blood draw site 
may occur, but can be prevented or lessened by applying pressure to the blood draw site for a 
few minutes after the blood is taken. IM injection may also cause transient discomfort and 
fainting. Drawing blood and IM injection may cause infection. The use of aseptic (sterile) 
technique will make infection at the site where blood will be drawn or where the study 
vaccination will be given extremely unlikely. 
There is a small amount of risk to subjects who report that they are in good health but who have 
an unknown health problem at the time of screening. This trial will screen by physical exam, 
history, vital signs and sedimentation rate. Baseline safety labs for white blood cells (WBC), 
hemoglobin (Hgb), platelets (PLT), alanine aminotransferase (ALT), total bilirubin (T. Bili), and 
creatinine (Cr) will be drawn prior to study vaccination but results will not be reviewed until 
after study vaccination. To minimize the risk, subjects will not receive the second study 
vaccination unless, the most recently evaluated clinical safety laboratory values obtained prior to 
the second study vaccination are Grade 2 or less and the subject does not meet any of the other 
criteria listed in Section 5.2.3. 
There is potential for AEs to occur more frequently in the adjuvanted vaccine groups [70] than in 
the non-adjuvanted group and there is potentially a higher risk for AEs to occur more frequently 
in the higher dose influenza antigen groups than in the lower dose viral antigen groups. The 


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monovalent A/H7N9 vaccine to be used in this study has not been tested for safety in animals 
and has not previously been evaluated in humans. The DMID, NIAID sponsored two Phase II 
clinical trials that included an assessment of the safety, reactogenicity, and immunogenicity of 
two IM doses of a monovalent A/H7N9 vaccine produced by Sanofi Pasteur, Swiftwater, PA, 
administered with or without AS03 in healthy adults (DMID Protocol 13-0032; NCT01938742 
and DMID Protocol 13-0033; NCT01942265).  
 
Overall, the study products administered in both of these clinical trials were generally safe and 
well-tolerated. For DMID Protocol 13-0032, nine SAEs were reported. All were assessed as 
being not related to study product. Two cases of Autoimmune thyroiditis (Hashimoto’s 
disease/Hashimoto’s thyroiditis) or 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) and the second 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 
to vaccination, but both disorders received the diagnosis after vaccination). 
 
The current monovalent split IIV was derived from the influenza virus A/Hong Kong/125/2017 
(H7N9).  The manufacturing process for the production of this investigational A/H7N9 vaccine 
is similar to the process used to produce the licensed Influenza Virus Vaccine Fluzone® family of 
products. As such, the safety profile of the candidate A/H7N9 vaccine should be similar to the 
current Fluzone® vaccine. 
 formulation has been 
determined by
 
 
 In this clinical trial, the labeling of the original 
 
 The vaccine preparation has been adjusted to 
meet the targeted concentration by 
 
 was produced in accordance with the commercial process
 
 
The final vaccine preparation is 
 
  
  
The potential risks to subjects are anticipated to be similar to those observed for Sanofi Pasteur’s 
unadjuvanted licensed inter-pandemic (seasonal) IIVs (Fluzone® and Fluzone® High-Dose), 
their unadjuvanted licensed 2009 A/H1N1 and A/H5N1 monovalent IIVs, and for previously 
conducted 2013 H7N9 IIV administered with and without AS03 and MF59 (see the Sanofi 


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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. 
During the swine influenza (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 
(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 


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vaccination, typically with onset within 6 weeks after vaccination [71]. Interestingly, although 
vaccination rates have increased in the last 10 years, the numbers of reported cases of vaccine-
associated GBS have declined [72]. A recent study in Canada showed that the 2009 H1N1 
vaccine was associated with a small but significant risk of GBS in persons 50 years and older 
[73]. An active, population-based surveillance study conducted in the United States during the 
2009-2010 influenza season found less than 1 excess GBS case per million doses of 2009 H1N1 
vaccine administered – a rate similar to that associated with some previously administered 
annual influenza vaccines [74-76]. Another study using the Medicare system showed an elevated 
risk of GBS with 2009 monovalent 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) [77]. An international collaboration study also supported a conclusion of an 
association between 2009 H1N1 vaccination and GBS [78]. It is unknown if the administration 
of the monovalent inactivated influenza 2017 H7N9 virus vaccine to be used in this clinical trial 
will result in an increased incidence of GBS as the mechanism leading to this AE has not been 
completely elucidated. 
As of November 22, 2015 (per the manufacturer’s IB dated February 2016), data are available 
for 56 GSK sponsored clinical trials of AS03-adjuvanted monovalent pandemic vaccines 
manufactured by GSK. More than 18,000 adults (age ≥18 years) and 6,900 pediatric (6 months to 
17 years old) clinical trial participants have received at least one dose of a GSK-manufactured, 
AS03-adjuvanted monovalent pandemic influenza vaccine. Clinical data collected by GSK as of 
November 22, 2015, suggest that inactivated monovalent (pre)pandemic influenza virus antigens 
adjuvanted with AS03 have generally acceptable safety and benefit/risk profiles, though the 
incidence rates of solicited local and systemic AEs are higher with AS03-adjuvanted antigens 
than with antigen alone, a licensed IIV3, or placebo. Some unsolicited AEs (e.g., insomnia, 
dizziness, cystitis) were associated with a higher relative risk among H5N1/AS03 recipients in 
contrast to Fluarix® or placebo recipients. 
The information and guidance that follow are based on pre-clinical and clinical study results for 
GSK-manufactured AS03-adjuvanted monovalent pandemic vaccines, post-marketing safety 
surveillance data seen with unadjuvanted, IIV3s and (in the case of the H1N1 vaccines) post-
marketing safety surveillance data seen to date for both Pandemrix™ and Arepanrix™ H1N1 
vaccines. 
The reactogenicity profile in humans of GSK-manufactured AS03-adjuvanted vaccines is 
primarily associated with the adjuvant. The incidence and severity of injection site redness, 
swelling, and pain at the injection site in recipients of AS03-adjuvanted vaccines are increased 
relative to monovalent pandemic influenza antigen alone, a licensed IIV3, or placebo. There is no 
increase in injection site and systemic reactogenicity events in recipients of AS03-adjuvanted 
vaccines after a second dose of vaccine relative to the first when given 21 days apart. In young 


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children (6 months to 6 years old), increased frequency of fever has been observed following a 
heterologous booster dose of adjuvanted vaccine administered 6 months after the primary series. 
As of November 22, 2015, there has been no evidence in clinical trials to support a conclusion 
that any potential immune-mediated disease or group of diseases was causally related to an AS03-
adjuvanted vaccine. There have been no deaths in GSK clinical trials of AS03-adjuvanted 
pandemic influenza vaccines assessed as related to study vaccine. A total of 1,428 non-fatal SAEs 
have been reported for adult subjects as of November 22, 2015. Fifteen of these events were 
deemed related to vaccination by the Investigator or GSK. Of these, six occurred in recipients of 
an adjuvanted H1N1 vaccine: asthma, herpes zoster, hepatic enzyme increased, and pain in 
extremity, polymyalgia rheumatic, and thrombocytopenia. Three occurred in recipients of 
unadjuvanted H1N1 vaccine: alanine aminotransferase increased, hypersensitivity, and multiple 
sclerosis. One SAE classified as related (myalgia) occurred in a subject who received a control 
product. Four SAEs classified as related occurred in recipients of an adjuvanted H5N1 vaccine: 
autoimmune hepatitis, angina pectoris, pulmonary embolism, and non-Hodgkin’s lymphoma. One 
SAE classified as related (lobar pneumonia) occurred in a recipient of an unadjuvanted H5N1 
vaccine. Overall, the reactogenicity and safety profile of AS03-adjuvanted pandemic vaccines is 
acceptable and no safety concerns have been identified in clinical trials. 
Narcolepsy is a chronic sleep disorder with a background incidence rate, based on US data, of 
approximately 1.37 per 100,000 per year, with a peak onset between 10 and 19 years of age in 
some datasets. Narcolepsy, when associated with cataplexy is seen almost exclusively in 
individuals who are HLA DQB1*0602 allele carriers [79]. An autoimmune etiology has been 
proposed. In the post-marketing period for adjuvanted H1N1 pandemic vaccines, several 
epidemiological studies conducted in several countries independently of GSK reported an 
increased risk of narcolepsy with or without cataplexy in subjects who were vaccinated with 
Dresden-manufactured H1N1 (Pandemrix™ H1N1) vaccine during the 2009-2010 season. These 
studies have described an absolute risk increase of narcolepsy of approximately 1.4 to 8 additional 
cases per 100,000 vaccinated children/adolescents, and approximately one additional case per 
100,000 vaccinated adults compared to background rates of 0.12 to 0.79 per 100,000 
children/adolescents per year and 0.67 to 1.10 per 100,000 adults per year. The observed temporal 
association between narcolepsy and vaccination with Pandemrix™ H1N1 is not fully understood, 
and further research to evaluate the association between narcolepsy and Pandemrix™ H1N1, and 
other possible contributory factors to the development of narcolepsy during the 2009-2010 
pandemic, such as genetic and environmental factors, is being conducted. A GSK-supported 
study was conducted in Quebec, Canada, to assess the risk of narcolepsy associated with 
Arepanrix H1N1, using various index dates, risk periods, observation periods, and 
epidemiological designs. Overall, GSK considers that there is no strong evidence of an 
association between Q-Pan-H1N1 and narcolepsy in Quebec.  Recently, the CDC conducted a 
study to assess trends in narcolepsy incidence rates before and after 2009 H1N1 influenza 


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(pH1N1) vaccination campaigns and to evaluate the risk of narcolepsy following adjuvanted 
pH1N1 vaccines. Results of the incidence rates analysis indicated no change in narcolepsy rates 
between the period before wild-type pH1N1 virus circulation and the period after the start of 
pH1N1vaccination campaigns in any countries except Sweden, the first signaling country, and 
Taiwan, where incidence began to increase upon wild-type pH1N1 virus circulation. In the case-
control analysis, no association was observed for AS03-adjuvanted pH1N1 vaccine and 
narcolepsy in children or adults, and in the case-coverage analysis, no association was observed 
for narcolepsy in children, the only age groups studied. However, the data for the AS03-
adjuvanted pH1N1 vaccine, Pandemrix™, were limited. (20th Annual Conference on Vaccine 
Research, April 24-26th, 2017, Abstract S6-1). 
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**, GBS* 
*Spontaneous reports of GBS syndrome have been received following vaccination 
with Arepanrix™ (H1N1); however, a causal association between vaccination and 
GBS has not been established. Data from a post-marketing epidemiological study in 
Canada indicate a small but significant increased relative risk of GBS 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. 


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


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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 H7N9 IIV in PBS with or 
without AS03 adjuvant. Vaccination using the 2017 H7N9 IIV with AS03 adjuvant may or may 
not provide protection against a serious disease with the influenza 2017 H7N9 virus, should the 
participant be exposed. The duration of any such protection is currently unknown. The 2017 
H7N9 IIV with or without AS03 adjuvant is not expected to offer protection against circulating 
seasonal influenza viruses. There may be pandemic preparedness benefits to society in the future 
if the vaccine and adjuvants being evaluated in this clinical trial prove to be sufficiently safe and 
immunogenic and can be employed if a need for widespread influenza 2017 H7N9 vaccination 
occurs. 


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3 
STUDY OBJECTIVES AND OUTCOME MEASURES 
3.1 
Study Objectives 
3.1.1 
Primary 
Safety: 
• To assess the safety and reactogenicity following sequential or simultaneous IM 
administration of 2 doses of AS03-adjuvanted 2017 H7N9 IIV and one dose of seasonal 
influenza vaccine (IIV4).  
Immunogenicity: 
• To assess the serum HAI and Neut antibody responses against A/H7N9 at approximately 
21 days following receipt of two doses of AS03-adjuvanted 2017 H7N9 IIV administered 
IM approximately 21 days apart. 
• To assess the serum HAI and Neut antibody responses against the seasonal influenza 
strains at approximately 21 days following receipt of IIV4. 
3.1.2 
Secondary  
Safety: 
• To assess unsolicited non-SAEs following sequential or simultaneous IM administration 
of AS03-adjuvanted 2017 H7N9 IIV and seasonal influenza vaccine (IIV4) 
• To assess MAAEs, including NOCMCs and PIMMCs, following sequential or 
simultaneous IM administration of AS03-adjuvanted 2017 H7N9 IIV and IIV4 
Immunogenicity: 
• To assess the HAI and Neut antibody responses at 21 days following receipt of 1 dose of 
AS03-adjuvanted 2017 H7N9 IIV. 
3.1.3 
Exploratory 
Immunogenicity: 


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• To assess the effects of age, sex, BMI, and receipt of prior year(s) seasonal influenza 
vaccine(s) on serum HAI antibody responses following receipt of two doses of AS03-
adjuvanted 2017 H7N9 IIV.  
• To assess the durability of the antibody response to the 2017 H7N9 study vaccine strain 
and the IIV4 strains at approximately 180 days following the second dose of AS03-
adjuvanted 2017 H7N9 IIV vaccine.  
• To assess the NA content of the 2017 H7N9 IIV and the licensed seasonal IIV4 and 
determine the serum antibody responses to NA following receipt of 2017 H7N9 IIV and 
licensed seasonal IIV4. 
3.2 
Study Outcome Measures 
3.2.1 
Primary 
Safety: 
• Occurrence of all SAEs following the first study vaccination through approximately 12 
months after the last study vaccination. 
• Occurrence of study vaccine-related SAEs following the first study vaccination through 
approximately 12 months after the last study vaccination. 
• Occurrence of solicited injection site and systemic AEs following each study vaccination 
through 7 days after each study vaccination. 
• Occurrence of clinical safety laboratory AEs following each study vaccination through 
approximately 7 days after each study vaccination. 
Immunogenicity: 
• For HAI and Neut antibodies, percentage of subjects achieving seroconversion against 
the 2017 H7N9 study vaccine strain (defined as either a pre-vaccination titer <1:10 and a 
post-vaccination titer ≥1:40 or a pre-vaccination titer ≥1:10 and a minimum four-fold rise 
in post-vaccination antibody titer) at approximately 21 days after 2 doses of AS03-
adjuvanted 2017 H7N9 IIV (Group 1– Day 43; Group 2 – Day 64; Group 3 – N/A). 
• For HAI and Neut antibodies, percentage of subjects achieving seroconversion against 
each of the study IIV4 strains at approximately 21 days after receipt of study IIV4 
(Groups 1, 2 and 3 – Day 22).  
• For HAI and Neut antibodies, percentage of subjects with an antibody titer of ≥1:40 
against the influenza 2017 H7N9 study vaccine strain at approximately 21 days following 


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receipt of 2 doses of AS03-adjuvanted 2017 H7N9 IIV (Group 1 – Day 43; Groups 2 – 
Day 64; Group 3 – N/A). 
• For HAI and Neut antibodies, percentage of subjects with an antibody titer of ≥1:40 
against each of the study IIV4 strains at approximately 21 days after receipt of study IIV4 
(Groups 1, 2 and 3 – Day 22).  
• GMTs of serum HAI and Neut antibodies against the 2017 H7N9 IIV strain at 
approximately 21 days following receipt of 2 doses of AS03-adjuvanted 2017 H7N9 IIV 
(Group 1– Day 43; Group 2 – Day 64; Group 3 – N/A).  
• GMTs of serum HAI and Neut antibodies against each of the 2017 IIV4 strains at 
approximately 21 days after receipt of IIV4 (Group 1, 2 and 3– Day 22). 
3.2.2 
Secondary 
Safety: 
• Occurrence of study vaccine-related unsolicited non-serious AEs following each study 
vaccination through approximately 21 days after each study vaccination. 
• Occurrence of all unsolicited non-SAEs following each study vaccination through 
approximately 21 days after each study vaccination.  
• Occurrence of MAAEs, including NOCMCs and PIMMCs, following the first study 
vaccination through approximately 12 months after the last study vaccination. 
Immunogenicity: 
• For HAI and Neut antibodies, percentage of subjects achieving seroconversion against 
the 2017 H7N9 vaccine strain at approximately 21 days after receipt of 1 dose of AS03-
adjuvanted 2017 H7N9 IIV (Group 1– Day 22; Group 2 – Day 43; Group 3 – N/A). 
• For HAI and Neut antibodies, percentage of subjects achieving serum HAI and Neut 
antibody titers ≥1:40 against the influenza 2017 H7N9 vaccine strain at baseline and 
approximately 21 days after receipt of 1 dose of AS03-adjuvanted 2017 H7N9 IIV 
(Group 1–Day 1 (baseline) and Day 22; Group 2 –Day 22 (baseline) and Day 43; Group 3 
– N/A). 
• GMTs of serum HAI and Neut antibodies against the influenza 2017 H7N9 vaccine virus 
at baseline and at approximately 21 days after receipt of 1 dose of AS03-adjuvanted 2017 
H7N9 IIV. (Group 1–Day 1 (baseline) and Day 22; Group 2 –Day 22 (baseline) and Day 
43; Group 3 – N/A). 


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3.2.3 
Exploratory 
Immunogenicity: 
• For HAI and Neut antibodies, percentage of subjects achieving seroconversion, 
percentage with titer ≥1:40 and the GMTs against the 2017 H7N9 study vaccine strain 
approximately 21 and 180 days after 2 doses of adjuvanted 2017 H7N9 IIV, stratified by 
age, sex, BMI, and prior receipt of seasonal influenza vaccine(s) for Groups 1 and 2. 
• For HAI and Neut antibodies, percentage of subjects achieving seroconversion, 
percentage with a titer ≥1:40 and the GMTs against the IIV4 vaccine strains 
approximately 21 and 180 days after receipt of IIV4, stratified by age, sex, BMI, and 
prior receipt of seasonal influenza vaccine(s). 
• For HAI and Neut antibodies, percentage of subjects achieving seroconversion, 
percentage with titer ≥1:40, and GMTs against the 2017 H7N9 study vaccine strain at 
approximately 180 days after 2 doses of adjuvanted 2017 H7N9 IIV for Groups 1 and 2. 
• Percentage of subjects with detectable levels of serum N1, N2 and N9 NA-specific 
antibody elicited by 2017 H7N9 and seasonal IIV4 vaccination, and the correlation of the 
NA content of 2017 H7N9 IIV and seasonal IIV4 with the elicited NA specific antibody 
responses at baseline and approximately 21 and 180 days after 2 doses of adjuvanted 
2017 H7N9 IIV for Groups 1 and 2; and approximately 21 and 180 days after receipt of 
the seasonal IIV4 vaccine for all Groups. 
 
 


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4 
STUDY DESIGN 
This is a randomized, un-blinded, Phase II study in males and non-pregnant females, who are in 
good health, 19 to 64 years of age. This clinical trial is designed to assess the safety, 
reactogenicity, and immunogenicity of a pre-pandemic AS03 (GSK) adjuvanted 2017 
monovalent inactivated influenza A/H7N9 vaccine (2017 H7N9 IIV) manufactured by Sanofi 
Pasteur (3.75 mcg of HA per dose) and Phosphate Buffered Saline (PBS) diluent, when two 
doses are administered 21 days apart either sequentially or simultaneously (within 15 minutes) 
with licensed seasonal influenza vaccine.  The 2017 H7N9 IIV was manufactured using a reverse 
genetics-derived reassortant candidate vaccine virus IDCDC RG56B (H7N9), containing the HA 
and NA from low pathogenic influenza A/Hong Kong/125/2017 (H7N9) and the PB2, PB1, PA, 
NP, M and NS from A/Puerto Rico/8/1934 (H1N1). IIV4 will be provided through the DMID 
CMS, Fisher BioServices. 
Subjects who are in good health and meet all eligibility criteria (including an ESR, urine or 
serum pregnancy test [female subjects], history and physical exam) within 28 days prior to the 
first vaccination or on the day of, but prior to, first vaccination, will be eligible for randomization 
into one of three treatment arms as shown in Table 1. Baseline clinical safety laboratories will be 
drawn prior to the first vaccine dose and will not be used to screen subjects for eligibility. 
Reactogenicity will be measured by the occurrence of solicited injection site and systemic 
reactions from the time of each study vaccination through 7 days after each study vaccination. 
Unsolicited non-serious AEs will be collected from the time of each study vaccination through 
approximately 21 days after each study vaccination. SAEs and MAAEs, including NOCMCs and 
PIMMCs, will be collected from the time of the first study vaccination through approximately 12 
months after the last study vaccination. Clinical laboratory evaluations for safety will be 
performed on venous blood collected prior to each study vaccination and approximately 7 days 
after each study vaccination. 
Immunogenicity testing will include performing HAI and Neut antibody assays against the 2017 
H7N9 vaccine virus on serum samples collected for Group 1 on Days 1 (baseline), 22, and 43, 
and at approximately 180 days post second adjuvanted 2017 H7N9 IIV dose (Day 202), and for 
Group 2 on Study Days 22 (baseline), 43, and 64, and at approximately 180 days post second 
2017 H7N9 IIV adjuvanted dose (Day 223).Serological antibody assays will be performed 
against the vaccine viruses in IIV4 from serum samples collected at baseline (Day 1) and 
approximately 21 and 180 days following receipt of IIV4 (Groups 1, 2, and 3).   
Novel methods for identifying and assessing alternative correlates of protection against influenza 
infection are needed.  To assess the NA-specific antibody response to vaccination, it is first 
necessary to determine the NA content of inactivated influenza vaccine; this assay is under 


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development.  If successful, the NA content in a dosage-specific manner can be correlated to the 
N9 NA-specific antibody responses elicited by the 2017 H7N9 IIV. 
Subjects will be ineligible to participate in this trial if they have received the 2017-2018 licensed 
seasonal IIV (IIV3 or IIV4, including high dose vaccine for the elderly) any time prior to 
enrollment; IIV4 will be provided at the first study vaccination to all participants in the study. 
For additional details on study procedures and evaluations and study schedule by study 
visits/days, see Sections 7 and 8 and Appendix A: Schedule of Study Procedures and 
Evaluations. 


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5 
STUDY ENROLLMENT AND WITHDRAWAL 
Approximately 150 individuals 19-64 years of age, males and non-pregnant females, who are in 
good health by history and meet all eligibility criteria, will be enrolled at up to 4 VTEU sites 
participating in this trial. The target population should reflect the community at large at each of 
the participating VTEU sites. Estimated time to complete enrollment in this trial is 
approximately 12 weeks. Information regarding this trial may be provided to potential subjects 
who have previously participated in vaccine trials conducted at the participating VTEU sites. 
Other forms and/or mechanisms of recruitment may also be used. The local IRB will approve all 
materials prior to use. 
Subject Inclusion and Exclusion Criteria must be assessed by a study clinician licensed to make 
medical diagnoses and listed on the Form FDA 1572 as the site principal investigator or sub-
investigator. 
No exemptions are granted on Subject Inclusion or Exclusion Criteria in DMID-sponsored 
studies. Questions about eligibility should be directed toward the DMID Medical Officer. 
5.1 
Eligibility Criteria 
5.1.1 
Subject Inclusion Criteria 
Subjects eligible to participate in this trial must meet all of the following inclusion criteria: 
1. Provide written informed consent prior to initiation of any study procedures. 
2. Are able to understand and comply with planned study procedures and be available for all 
study visits. 
3. Are males or non-pregnant females, 19 -64 years of age, inclusive. 
4. Are in good health1. 
1As determined by medical history and physical examination to evaluate acute or currently ongoing chronic medical 
diagnoses or conditions, defined as those that have been present for at least 90 days, which would affect the assessment 
of the safety of subjects or the immunogenicity of study vaccinations. Chronic medical diagnoses or conditions should 
be stable for the last 60 days (no hospitalizations, Emergency Room (ER), or urgent care for condition and no adverse 
symptoms that need medical intervention such as medication change/supplemental oxygen). This includes no change in 
chronic prescription medication, dose, or frequency as a result of deterioration of the chronic medical diagnosis or 
condition in the 60 days prior to enrollment. Any prescription change that is due to change of health care provider, 
insurance company, etc., or that is done for financial reasons, as long as in the same class of medication, will not be 
considered a deviation of this inclusion criterion. Any change in prescription medication due to improvement of a 
disease outcome, as determined by the site principal investigator or appropriate sub-investigator, will not be 
considered a deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the 
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or assessment of reactogenicity and immunogenicity and do not indicate a worsening of medical diagnosis or 
condition. Similarly, medication changes subsequent to enrollment and study vaccination are acceptable provided 
there was no deterioration in the subject’s chronic medical condition that necessitated a medication change, and there 
is no additional risk to the subject or interference with the evaluation of responses to study vaccination. Note: Topical, 
nasal, and inhaled medications (with the exception of inhaled corticosteroids as outlined in the Subject Exclusion 
Criteria [see Section 5.1.2]), herbals, vitamins, and supplements are permitted. 
5. Oral temperature is less than 100.0°F. 
6. Pulse is 47 to 100 beats per minute (bpm), inclusive. 
7. Systolic blood pressure is 85 to 150 mmHg, inclusive (subjects <65 years of age), 85 to 
160 mmHg, inclusive (subjects > 65 years of age). 
8. Diastolic blood pressure is 55 to 95 mmHg, inclusive. 
9. ESR is less than 30 mm per hour. 
10. Women of childbearing potential2 must use an acceptable contraception method3 from 30 
days before first study vaccination until 60 days after last study vaccination. 
2Not sterilized via tubal ligation, bilateral oophorectomy, salpingectomy, hysterectomy, or successful Essure® 
placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at 
least 90 days after the procedure, and still menstruating or <1 year of the last menses if menopausal. 
3Includes, non-male sexual relationships, abstinence from sexual intercourse with a male partner, monogamous 
relationship with vasectomized partner who has been vasectomized for 180 days or more prior to the subject receiving 
the first study vaccination, barrier methods such as condoms or diaphragms with spermicide or foam, effective 
intrauterine devices, NuvaRing®, and licensed hormonal methods such as implants, injectables, or oral contraceptives 
(“the pill”). 
11. Women of childbearing potential must have a negative urine or serum pregnancy test 
within 24 hours prior to study vaccination. 
5.1.2 
Subject Exclusion Criteria 
Subjects eligible to participate in this trial must not meet any of the following exclusion criteria: 
1. Have an acute illness4, as determined by the site principal investigator or appropriate sub-
investigator, within 72 hours prior to study vaccination. 
4An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion 
of the site principal investigator or appropriate sub-investigator, the residual symptoms will not interfere with the 
ability to assess safety parameters as required by the protocol. 
2. Have any medical disease or condition that, in the opinion of the site principal 
investigator or appropriate sub-investigator, is a contraindication to study participation5. 
5Including acute or chronic medical disease or condition, defined as persisting for at least 90 days, that would place 
the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may 
interfere with the evaluation of responses or the subject’s successful completion of this trial. 


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3. Have immunosuppression as a result of an underlying illness or treatment, a recent 
history or current use of immunosuppressive or immunomodulating disease therapy.  
4. Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to 
study vaccination. 
5. Have known active neoplastic disease or a history of any hematologic malignancy. Non-
melanoma, treated, skin cancers are permitted. 
6. Have known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection. 
7. Have known hypersensitivity or allergy to eggs, egg or chicken protein, squalene-based 
adjuvants, or other components of the study vaccine. 
8. Have a history of severe reactions following previous immunization with licensed or 
unlicensed influenza vaccines. 
9. Have a personal or family history of narcolepsy. 
10. Have a history of 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. 
13. Have a history of alcohol or drug abuse within 5 years prior to study vaccination. 
14. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric 
diagnosis that may interfere with subject compliance or safety evaluations. 
15. Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement 
for danger to self or others within 10 years prior to study vaccination. 
16. Have taken oral or parenteral (including intra-articular) corticosteroids of any dose within 
30 days prior to study vaccination. 
17. Have taken high-dose inhaled corticosteroids7 within 30 days prior to each study 
vaccination. 
7High-dose defined per age as using inhaled high dose per reference chart https://www.nhlbi.nih.gov/health-
pro/guidelines/current/asthma-guidelines/quick-reference-html#estimated-comparative-daily-doses  
18. Received a licensed live vaccine within 30 days prior to the first study vaccination, or 
plan to receive a licensed live vaccine within 30 days before or after each study 
vaccination. 
19. Received or plan to receive a licensed, inactivated, vaccine (excluding all flu vaccines) 
within 14 days before or after each study vaccination.  


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20. Received or plan to receive the 2017-2018 inactivated seasonal flu vaccine prior to or 
during the clinical trial and for the remainder of the 2017-2018 season.  
21. Received Ig or other blood products (with exception of Rho D Ig) within 90 days prior to 
each study vaccination. 
22. Received an experimental agent8 within 30 days prior to the first study vaccination, or 
expect to receive an experimental agent9 during the 13-month trial-reporting period. 
8Including vaccine, drug, biologic, device, blood product, or medication. 
9Other than from participation in this trial. 
23. Are participating or plan to participate in another clinical trial with an interventional 
agent10 that will be received during the 13-month trial-reporting period. 
10Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication. 
24. Received or plan to receive an influenza A/H7 vaccine11 or have a history of influenza 
A/H7 subtype infection.  
11And assigned to a group receiving influenza A/H7 vaccine. 
25. Have traveled to mainland China and had substantial12 direct contact with live or freshly 
slaughtered poultry or pigeons within the past five years. 
12Substantial contact is defined as visited a poultry farm and/or a live poultry market.  
26. Occupational exposure to or substantial direct physical contact13 with birds in the past 
year and through the 21 days after the last study vaccination. 
13Exposure to free range chickens in the yard is exclusionary. Casual contact with birds at petting zoos or county or 
state fairs, or having pet birds does not exclude subjects from study participation. 
27. Female subjects who are breastfeeding or plan to breastfeed at any given time from the 
first study vaccination until 30 days after the last study vaccination. 
28. Plan to travel outside the US (continental US, Hawaii, and Alaska) from enrollment 
through 21 days after the last study vaccination. 
5.2 
Treatment Assignment Procedures 
5.2.1 
Enrollment and Randomization Procedures 
Per ICH guideline E6: Good Clinical Practice (GCP), screening records will be kept at each 
participating VTEU site to document the reason why an individual was screened, but failed trial 
entry criteria. The reasons why individuals failed screening will be recorded in the Statistical and 
Data Coordinating Center’s (SDCC) AdvantageEDCSM (Electronic Data Capture System). 


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Once consented and upon entry of demographic data and confirmation of eligibility for this trial, 
the subject will be enrolled and randomly assigned to one of three treatment arms. Subjects in 
Groups 1 and 2 will receive three vaccinations. Subjects in Group 3 will receive IIV4 as an 
unblinded comparator. Subjects will be randomized with allocation 2:2:1 into three treatment 
arms (see Table 1), stratified by clinical site.  
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.  
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 an un-blinded clinical trial. 
Subjects, investigators, study personnel performing any study-related assessments following 
study vaccine administration are not blinded to study treatment. However, laboratory personnel 
performing HAI and Neut antibody assays will receive serum samples blinded to subject ID 
number and sample visit number. 
The randomization scheme will be generated by the SDCC and each subject’s treatment 
assignment will be displayed in AdvantageEDC upon enrollment. 
The Data and Safety Monitoring Board (DSMB) may receive data in aggregate and presented by 
treatment arm, including expected and observed rates of the expected AEs. The DSMB will 
review grouped data in the closed session only. 
5.2.3 
Reasons for Withdrawals and Discontinuation of Treatment 
Subjects may voluntarily withdraw their consent for trial participation at any time and for any 
reason, without penalty. 
A subject may withdraw or be withdrawn from this trial for any of the following reasons: 


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• Medical disease or condition, or any new clinical finding for which continued 
participation, in the opinion of the site principal investigator or appropriate sub-
investigator, would compromise the safety of the subject, or would interfere with the 
subject's successful completion of this trial, or would interfere with the evaluation of 
responses (for example, has baseline significant laboratory abnormalities). 
• Subject no longer meets eligibility criteria (see Section 5.1). Note: Medication changes in 
the 60 days prior to enrollment, as specified in Subject Inclusion Criterion #4, are 
exclusionary for receipt of the first study vaccination only. 
• As deemed necessary by the site principal investigator or appropriate sub-investigator for 
noncompliance or other reasons. 
• Subject withdrawal of consent. 
• Subject lost to follow-up. 
• Termination of this trial. 
• New information becomes available that makes further participation unsafe. 
The second and/or third dose will not be administered to a subject if any of the following criteria 
are met: 
• Medical condition or medication change for which continued participation, in the opinion 
of the site principal investigator or appropriate sub-investigator, would pose a risk to the 
subject or would be likely to confound interpretation of the results. 
• Presence of signs or symptoms that could confound or confuse assessment of study 
vaccine reactogenicity. For subjects with injection site or systemic signs or symptoms, or 
with an acute illness, including an oral temperature greater than or equal to 100°F, the 
subsequent study vaccination should be postponed/deferred until signs, symptoms, or 
acute illness have resolved, or are improving as further specified below, and if within the 
acceptable protocol-specified window for Dose 2 (Group 1 and Group 2, Day 22+7), or 
Dose 3 (Group 2, Day 43+7). No exceptions to the protocol-specified window will be 
made. Note for afebrile, acute illness only: If a subject is afebrile, his/her acute illness is 
nearly resolved with only minor residual symptoms remaining, this occurs within the 
acceptable protocol-specified window for Dose 2 (Group 1 and Group 2, Day 22+7), or 
Dose 3 (Group 2, Day 43+7) and, in the opinion of the site principal investigator or 
appropriate sub-investigator, the residual symptoms will not interfere with the ability to 
assess safety parameters as required by the protocol, the subject may receive the 
subsequent study vaccination without further approval from the DMID Medical Officer. 
No exceptions to the protocol-specified window will be made.  


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• Grade 3 solicited or unsolicited AE that is ongoing, whether or not it is improved or 
resolving.  
• Any unresolved or continuing Grade 2 AE that has not decreased in severity to Grade 1 
or less.  
• An unresolved or continuing Grade 1 AE is permissible following the documented 
determination by the site principal investigator or appropriate sub-investigator, that it 
would not render study vaccination unsafe or interfere with the evaluation of responses. 
• Grade 3 solicited or unsolicited AE that occurs without alternative etiology in the 8 days 
following each study vaccination. 
• Grade 3 clinical safety laboratory value (according to the toxicity table, Section 9.2.3) 
that does not decrease to Grade 2 or less prior to the second study vaccination. Any 
clinical safety laboratory parameter may be re-evaluated only once at the central (clinical) 
laboratory in order to assess eligibility prior to the next study vaccination. If the clinical 
safety laboratory value decreases to Grade 2 or less, the subject may receive the next 
study vaccination. The subsequent study vaccination should be scheduled to occur within 
the acceptable protocol-specified window for the Dose 2 (Group 1 and Group 2, Day 
22+7), or Dose 3 (Group 2, Day 43+7). No exceptions to the protocol-specified window 
will be made. 
• New onset of illness or condition that meets the Subject Exclusion Criteria (see Section 
5.1.2). 
• Hospitalization that occurs before administration of the second or third study vaccination.  
• Subject no longer meets eligibility criteria (see Section 5.1). Note: Medication changes 
subsequent to the first study vaccination are not exclusionary for receipt of the second 
study vaccination provided there was no deterioration in the subject’s chronic medical 
condition that necessitated a medication change, and there is no additional risk to the 
subject or interference with the evaluation of responses to study vaccination. 
• As deemed necessary by the site principal investigator or appropriate sub-investigator for 
noncompliance or other reasons. 
• Subject refusal of further study vaccination. 
• Subject withdrawal of consent. 
• Subject lost to follow-up. 
• Termination of this trial. 
• New information becomes available that makes further participation unsafe. 


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5.2.4 
Handling of Withdrawals and Discontinuation of Treatment 
The primary reason for withdrawal from this trial will be recorded on the Study Status data 
collection form (DCF). Subjects will be encouraged to complete the Early Termination Visit. 
The Early Termination Visit procedures are listed in Section 8.5. 
Although subjects are free to withdraw at any time or may be withdrawn by the site principal 
investigator or appropriate sub-investigator at any time (see Section 5.2.3), those subjects do not 
receive Dose 2 or Dose 3 of study vaccine will be encouraged to remain in this trial for follow-up 
safety assessments (may be conducted by phone call rather than in person) continuing through 
approximately 12 months after their last study vaccination. These subjects will also be 
encouraged to provide a venous blood sample for immunogenicity assays at approximately 21 
days and 180 days after their last study vaccination, if applicable. See the protocol-specific 
Manual of Procedures (MOP) for alternate follow-up requirements. 
Every attempt will be made to follow all AEs, including solicited injection site and systemic 
reactions, unsolicited non-serious AEs, SAEs 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 
certified letter) will be made to locate or recall them, or at least to determine their health status. 
These efforts will be documented in the subject’s study records. 
Subjects who withdraw, or are withdrawn or terminated from this trial, or are lost to follow-up 
after signing the informed consent form (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. 
5.2.5 
Termination of Study 
Although the sponsor has every intention of completing this trial, it reserves the right to 
terminate this trial at any time for clinical or administrative reasons. Reasons for termination 
include, but are not limited to, study closure due to DSMB review and recommendation and at 
the discretion of DMID. 


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6 
STUDY INTERVENTION/INVESTIGATIONAL 
PRODUCT 
6.1 
Study Product Description 
2017 H7N9 IIV 
Sanofi Pasteur has developed a monovalent 2017 H7N9 IIV manufactured from a reverse 
genetics-derived reassortant virus containing the HA and NA from influenza A/Hong 
Kong/125/2017 (H7N9) and the PB2, PB1, PA, NP, M and NS from A/Puerto Rico/8/1934 
(H1N1).  The manufacturing process for the production of this monovalent 2017 A/H7N9 
IIV is similar to the manufacturing process used to produce the licensed IIV Fluzone® family 
of products.  
The HA content of the A/H7N9 vaccine formulation has been determined by 
 
In 
this clinical trial, the labeling of the original 
 
 The vaccine preparation has been adjusted to
 
 
The final vaccine preparation is 
 
  
PBS diluent 
The PBS diluent was produced in accordance with the commercial process utilized in 
manufacture of 
 buffer/diluent for the formulation of Fluzone®, influenza virus 
vaccine.  
AS03 Adjuvant [Adjuvant System AS(03)] 
AS03 is GSK’s proprietary 
Fluzone® Quadrivalent Influenza Vaccine (IIV4)  
IIV4 manufactured by Sanofi Pasteur for IM injection is an inactivated influenza vaccine, 
prepared from influenza viruses propagated in embryonated chicken eggs.  Fluzone® 
Quadrivalent is formulated to contain HA of each of the following four influenza strains 
recommended for the 2017-2018 influenza season: A/Michigan/45/2015 X-275 (H1N1), 
A/Hong Kong/4801/2014 X-263B (H3N2), B/Phuket/3073/2013 (B Yamagata lineage), and 
B/Brisbane/60/2008 (B Victoria lineage). The single-dose, pre-filled syringe (0.5 mL) 


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without thimerosal, clear plunger rod, without needle will be supplied as package of 10 
syringes.  
6.1.1 
Acquisition 
2017 H7N9 IIV will be provided by Sanofi Pasteur under contract to BARDA/DHHS.  
The PBS diluent will be provided by Sanofi Pasteur under contract to BARDA/DHHS. 
AS03 adjuvant will be provided by GSK under contract to BARDA/DHHS.  
Fluzone® Quadrivalent Influenza Vaccine (IIV4) will be provided through the DMID Clinical 
Materials Services (CMS) Contract, Fisher BioServices.  
Upon request by DMID, 2017 H7N9 IIV, PBS diluent, and AS03 adjuvant will be transferred to 
the following address: 
DMID Clinical Materials Services Contract 
Fisher BioServices 
20439 Seneca Meadows Parkway 
Germantown, MD 20876 
Phone: 240-477-1350 
Fax: 240-477-1360 
Email: DMID.CMS@ThermoFisher.com 
Sterile empty vials will be obtained by the DMID Clinical Materials Services (CMS), Fisher 
BioServices. 
2017 H7N9 IIV, AS03 adjuvant, PBS diluent, IIV4 and sterile empty vials for study vaccine 
preparation will be provided through the DMID CMS to the participating VTEU sites prior to the 
start of this trial upon request and with prior approval from DMID. Should the site principal 
investigator require additional 2017 H7N9 IIV, PBS diluent, AS03 adjuvant, IIV4 or sterile 
empty vials during this trial, further instructions are provided in the protocol-specific MOP. 
6.1.2 
Formulation, Storage, Packaging, and Labeling 
2017 H7N9 IIV 
Investigational influenza virus A/Hong Kong vaccine (H7N9), a monovalent type A inactivated 
vaccine for IM use, is a sterile suspension prepared from pandemic influenza virus candidate 
vaccine propagated in embryonated chicken eggs. The vaccine contains no preservative 
(thimerosal).  No components of this vaccine contain latex. It is essentially clear and slightly 
opalescent in color and is supplied in single-dose glass vials. The vials must be stored at 2°C to 
8°C (36°F to 46°F). Do not freeze. Vials will be provided with latex-free stoppers.  


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The specific mixing instructions are included in the MOP to achieve specific doses. 
Please note the difference 
 in the vial.   
 
  
 
 
 
PBS Diluent 
The 
 is provided as 
 
 
 It is essentially 
, and should be stored 
 The 
PBS diluent will be provided in 
 
 
AS03 Adjuvant [Adjuvant System (03)] 
The AS03 adjuvant is supplied as a preservative-free, oil-in-water, whitish to yellowish 
homogenous milky liquid emulsion in single-use 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.  
 
Fluzone® Quadrivalent Influenza Vaccine (IIV4) Fluzone® Quadrivalent Influenza Vaccine, 
Sanofi Pasteur, pre-filled syringes, thimerosal-free, 0.5 mL single-dose prefilled syringes (pack 
of 10). The pre-filled syringes must be stored at 2°C to 8°C (36°F to 46°F). Do not freeze. 
 
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 IBs for the 2017 H7N9 IIV, AS03 
adjuvant, and IIV4 as well as in the protocol-specific MOP. 
Sterile empty vials will be provided with latex-free stoppers. 
6.1.3 
Study Product Storage and Stability Procedures 
The temperature of the storage unit must be manually recorded daily (excluding non-business 
days and holidays as applicable) and continuously monitored and recorded during the duration of 
this trial per the participating VTEU site standard operating procedures (SOPs), and 
documentation will be maintained. If the temperature fluctuates outside of the required range, the 


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affected study product(s) must be quarantined at the correct storage temperature and labeled as 
‘Do Not Use’ (until further notice). The research pharmacist must alert the site principal 
investigator and study coordinator if the temperature fluctuates outside of the required range. In 
the event the temperature fluctuates outside of the required range, including accidental deep-
freezing or disruption of the cold chain, the affected study product(s) must not be administered. 
The site principal investigator or responsible person should immediately contact the DMID 
Product Support Team at DMIDProductSupportTeam@niaid.nih.gov for further instructions 
before any additional study vaccinations are administered. Based on the information collected, 
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. 
6.2 
Dosage, Preparation, and Administration of Study Intervention/ 
Investigational Product 
See the protocol-specific MOP Appendices for detailed information on the preparation, labeling, 
storage, and administration of study vaccine for each treatment arm. Study vaccine preparation 
will be performed by the participating VTEU site research pharmacist on the same day of study 
vaccine administration.  
Visually inspect the 2017 H7N9 IIV, PBS diluent, IIV4 and AS03 adjuvant upon receipt and 
prior to use. If the study product(s) appear(s) to have been damaged, contaminated or discolored, 
contain visible particulate matter or if there are any concerns regarding its integrity, do NOT use 
the affected study product(s). The affected study product(s) must be quarantined at 2°C to 8°C 
(36°F to 46°F) and labeled as ‘Do Not Use’ (until further notice). The site principal investigator 
or responsible person should immediately contact the DMID Product Support Team at 
DMIDProductSupportTeam@niaid.nih.gov and DMID Clinical Project Manager for further 
instructions before any additional study vaccinations are administered. Based on the information 
collected, DMID and/or the manufacturer will determine whether the affected study product(s) 
can be used. If it cannot be used, the site will receive specific instructions on how to return the 
affected study product(s) to the DMID CMS or destroy it on site. If the 2017 H7N9 vaccine, PBS 
diluent, or the AS03 adjuvant is unusable, study personnel will use another vial from the study 
supply. Replacement vials may be requested by contacting DMID. Additional instructions for 
quarantine and DMID contact information are provided in the protocol-specific MOP. 
For those doses that must be admixed, visually inspect the 2017 H7N9 IIV/PBS diluent plus 
adjuvant admixture prior to use. The admixture will be milky in appearance. If it appears to have 
been damaged, contaminated or discolored, contain visible particulate matter, or if there are any 
concerns regarding its integrity, do NOT use it. The affected 2017 H7N9 IIV/PBS diluent plus 


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adjuvant admixture must be quarantined at room temperature and labeled as ‘Do Not Use’ (until 
further notice). The site principal investigator or responsible person should immediately contact 
the DMID Product Support Team at DMIDProductSupportTeam@niaid.nih.gov and DMID 
Clinical Project Manager for further instructions before any additional study vaccinations are 
administered. Based on the information collected, DMID and/or the manufacturer will determine 
whether the 2017 H7N9 IIV/PBS diluent plus adjuvant admixture can be used. If it cannot be 
used, the site will receive specific instructions on how to send the 2017 H7N9 IIV/PBS diluent 
plus adjuvant admixture to the DMID CMS or destroy it on site. If the 2017 H7N9 IIV/PBS 
diluent plus adjuvant admixture is unusable, the participating VTEU sites’ research pharmacist 
will prepare another vial. Additional instructions for quarantine and DMID contact information 
are provided in the protocol-specific MOP. 
For those doses that must be admixed, the 2017 H7N9 IIV/PBS diluent plus adjuvant admixture, 
once mixed, must be stored at room temperature in an upright position and must be used within 8 
hours. Gently invert the final mixed vial 5 to 7 times immediately before the single dose is 
withdrawn.  Do not shake the final mixed vial.  Only one dose should be withdrawn from the 
final mixed vial. 
Study vaccine administration will be performed by a study personnel member who is 
credentialed to administer vaccines and may also participate in dose preparation, and may be 
involved in study-related assessments or have subject contact for data collection following study 
vaccine administration.  
 
For treatment assignment per Group, refer to Table 1.  
On study Day 1, Groups 1-3 will receive Dose 1. For Group 1, Dose 1 consists of one 
vaccination of AS03-adjuvanted 2017 H7N9 IIV and one vaccination of licensed seasonal IIV4 
in the deltoid muscle of opposite arms. This is the only Group, and the only study Day for Group 
1, that subjects will receive two vaccines administered IM simultaneously (within 15 minutes of 
each other). On Day 1, Group 2 and Group 3 will receive one vaccination of IIV4 administered 
IM in the deltoid muscle of the subject’s preferred arm.   
On study Day 22, Group 1 will receive the second dose of adjuvanted 2017 H7N9 IIV, and 
Group 2 will receive the first dose of adjuvanted 2017 H7N9 IIV. 
On Day 43, Group 2 will receive the second dose of adjuvanted 2017 H7N9 IIV. 
All study vaccinations will be administered as a 0.5 mL IM injection. The site of each injection 
(right and/or left arm) will be recorded on the appropriate DCF.  


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Aseptic technique will be used for the withdrawal and administration of each dose of study 
vaccine using a disposable sterile needle appropriate in length for each subject and a disposable 
sterile 1 mL syringe. See the protocol-specific MOP for information on how to administer IM 
injections. Each dose of study vaccine must be administered within 30 minutes of drawing into 
the syringe (not to exceed 8 hours total since admixing time), and the prepared syringe must be 
stored at room temperature until administered.  
Dose calculations are based on the actual HA content per 0.5 mL. Each 0.5 mL dose of AS03 
adjuvanted study vaccine contains one 0.25 mL dose of AS03 adjuvant. 
For Fluzone Quadrivalent, before administering a dose of vaccine, shake the prefilled syringe. 
Aseptic technique will be used for the administration of each dose of study vaccine using a 
disposable sterile needle appropriate in length for each subject. 
Subjects will be observed in the clinic for at least 20 minutes after the vaccination (for Group 1, 
Dose 1, the 20 minute clock will start after receipt of the second vaccination). The 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. 
6.3 
Modification of Study Intervention/Investigational Product for a 
Subject 
There will be no dose modifications. If a subject’s study vaccination is deferred, it should be 
rescheduled to occur within the acceptable protocol-specified window for that visit. No 
exceptions to the protocol-specified window will be made. 
  
6.4 
Accountability Procedures for the Study Intervention/ 
Investigational Product 
After receipt of the 2017 H7N9 IIV, PBS diluent, AS03 adjuvant, IIV4 and sterile empty vials, 
the site principal investigator is responsible for study product distribution and disposition, and 
has ultimate responsibility for study product accountability. The site principal investigator may 
delegate to the participating VTEU sites’ research pharmacist responsibility for study product 
accountability. The participating VTEU sites’ research pharmacist will be responsible for 
maintaining complete records and documentation of study product receipt, accountability, 
dispensation, storage conditions, and final disposition of the study product(s). The study product 
accountability records and dispensing logs will also capture vial numbers, including final mixed 


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vial number, date of study vaccine preparation/administration, time of study vaccine preparation, 
expiration of study vaccine preparation, time study vaccine is drawn into the syringe, and amount 
of study vaccine withdrawn for administration. Time of study vaccine administration to the 
subject will be captured on the appropriate DCF. All study product(s), including the amount of 
2017 H7N9 IIV, AS03 adjuvant, IIV4 and admixture, whether administered or not, must be 
documented on the appropriate study product accountability record or dispensing log. The 
sponsor's monitoring staff will verify the participating VTEU sites’ study product accountability 
records and dispensing logs per the site monitoring plan. 
Used and unused vials of 2017 H7N9 IIV, AS03 adjuvant, IIV4 and admixture will be retained 
until monitored and released for disposition as applicable. The pre-filled IIV4 single use syringe 
will be disposed of per site processes once the vaccine is administered. This can occur on an 
ongoing basis for used vials of 2017 H7N9 IIV, AS03 adjuvant, IIV4 and admixture. Used vials 
of A/H7N9 vaccine, AS03 adjuvant and admixture may be destroyed in accordance with site-
specific SOPs following each monitoring visit where Study Product Accountability is monitored, 
and resolution of any discrepancies. Final disposition of the unused 2017 H7N9 IIV, AS03 
adjuvant, IIV4 and sterile empty vials will be determined by DMID and communicated to the 
participating VTEU sites by the DMID Clinical Project Manager. 
6.5 
Assessment of Subject Compliance with Study Intervention/ 
Investigational Product 
Study product will be administered to subjects by a study vaccine administrator via IM injection 
at all dosing times according to subject treatment assignment and as described in Section 6.2. 
Thus, subject compliance is not anticipated to be an issue. There will be no dose schedule 
modifications, other than within the protocol-specified windows, as described in Section 6.3. 
6.6 
Concomitant Medications/Treatments 
Administration of any 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 the last study vaccination 
or early termination (if prior to 21 days after the last study vaccination), whichever occurs first. 
Medications reported in the electronic case report form (eCRF) are limited to those taken within 
30 days prior to the first study vaccination through approximately 21 days after the last study 
vaccination. Prescription and over-the-counter drugs will be included as well as herbals, 
vitamins, and supplements. In addition, receipt of non-study influenza vaccines will be solicited 
through approximately 180 days after the last study vaccination, and reported in the eCRF. Use 
of a new medication should prompt evaluation for the occurrence of any MAAE, including a new 
diagnosis of chronic medical disease or condition. 


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Medications that might interfere with the evaluation of the investigational product(s) should not 
be used during the trial-reporting period (approximately 12 months after the last study 
vaccination) unless clinically indicated as part of the subject’s health care. Medications in this 
category include the prohibited medications per the Subject Exclusion Criteria (see Section 
5.1.2). In addition, the site principal investigator or appropriate sub-investigator may identify 
other medications that should not be used due to a risk to subject safety or assessment of 
reactogenicity and immunogenicity. 


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7 
STUDY PROCEDURES AND EVALUATIONS 
7.1 
Clinical Evaluations 
Complete medical history will be obtained by interview of subjects at the screening visit 
(optional) or on Day 1 prior to the first study vaccination. Subjects will be queried regarding a 
history of significant medical disorders of the head, eyes, ears, nose, throat, mouth, 
cardiovascular system, lungs, gastrointestinal tract, liver, pancreas, kidney, urologic system, 
nervous system, blood, lymph nodes, endocrine system, musculoskeletal system, skin, and 
genital/reproductive tract. A history of any allergies, cancer, immunodeficiency, psychiatric 
illness, substance abuse, and autoimmune disease will be solicited. Subjects will also be queried 
regarding a personal history and family history of narcolepsy. At follow-up visits after the first 
study vaccination, an interim medical history will be obtained by interview of subjects noting 
any changes since the previous clinic visit or contact. The interim medical history should include 
an assessment for new medical conditions and symptoms suggestive of PIMMCs. 
Concomitant medications will be collected as described in Section 6.6. 
At the screening visit (optional) or the baseline visit (Day 1), a physical examination will be 
performed on all subjects to include the following organs and organ systems: skin, head and 
neck, lungs, heart, liver, spleen, extremities, lymph nodes, and nervous system, by a study 
clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as the site 
principal investigator or sub-investigator. At follow-up visits after the first, second, and/or third 
study vaccinations, a targeted physical examination may be performed, if indicated based on the 
subject’s interim medical history, by a study clinician licensed to make medical diagnoses and 
listed on the Form FDA 1572 as the site principal investigator or sub-investigator. Targeted 
physical examinations should also include an assessment for signs suggestive of PIMMCs. 
Vital signs (oral temperature, pulse, and blood pressure) will be collected at the screening visit 
(optional) and prior to each study vaccination (Day 1, and approximately Days 22 and 43, as 
applicable to study group). Vital signs assessed on Day 1 prior to the first study vaccination will 
be considered as baseline. Subjects must not eat or drink anything hot or cold, or smoke within 
10 minutes prior to taking oral temperature. 
Height and weight will be collected at the screening visit (optional) or on Day 1 prior to the first 
study vaccination for the calculation of BMI. 
Reactogenicity assessments will include an assessment of solicited AEs occurring from the time 
of each study vaccination through Day 8 after each study vaccination, which includes an 
assessment of injection site reactions including pruritus (itching), ecchymosis (bruising), 


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erythema (redness), induration (hardness), edema (swelling), pain, and tenderness as well as 
systemic reactions including fever, feverishness (chills/shivering/sweating), fatigue (tiredness), 
malaise (general unwell feeling), myalgia (body aches/muscular pain exclusive of the injection 
site), arthralgia (joint pain exclusive of the injection site), headache, and nausea. Pre-
administration reactogenicity assessments will be performed prior to each study vaccination to 
establish baseline, then the study vaccination will be given (see Section 5.2.3). 
Subjects will be observed in the clinic for at least 20 minutes after each study vaccination. The 
study vaccination site will be examined, post-administration reactogenicity assessments will be 
performed, and any AE/SAEs will be recorded on the appropriate DCF prior to discharge from 
the clinic. The study vaccination site will also be examined approximately 7 days after each 
study vaccination. 
All subjects will complete a subject memory aid from the time of each study vaccination through 
7 days after each study vaccination. Subject memory aids will be reviewed with the subjects for 
AEs (solicited injection site and systemic reactions and unsolicited AEs) approximately 3 and 7 
days after each study vaccination via phone call (Day 4) and clinical visit (Day 8). 
7.2 
Laboratory Evaluations 
7.2.1 
Clinical Laboratory Evaluations 
Urine or serum pregnancy tests will be performed locally by site laboratory at the screening visit 
(optional) and within 24 hours prior to each study vaccination on all women of childbearing 
potential. Results must be negative and known prior to randomization on Day 1 and 
administration of each study vaccination to be eligible for participation in this trial and receipt of 
each study vaccination. ESR will be collected from each subject at screening (optional) (within 
28 days prior to the first study vaccination) or on Day 1 prior to study vaccination to confirm 
trial eligibility. To be eligible for participation in this trial and receipt of the first study 
vaccination, the subject’s ESR evaluation must be confirmed to meet the eligibility criteria as 
outlined in the Subject Inclusion Criteria (see Section 5.1.1). 
• The ESR evaluation will be performed locally by the site. A venous blood sample 
(approximately 4 mL) will be collected from each subject at the baseline visit. 
Clinical safety laboratory parameters (WBC, Hgb, PLT, ALT, T. Bili, Cr) will be collected from 
each subject prior to each study vaccination and approximately 7 days after each study 
vaccination. These evaluations will be performed by the central (clinical) laboratory. Venous 
blood samples (approximately 10 mL) will be collected for each of these safety labs. The results 


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from the clinical safety laboratory parameters collected on Day 1 will not be available or 
reviewed prior to study vaccination, and will serve as a safety baseline assessment only. 
The volume of venous blood to be collected for ESR as well as clinical safety laboratory 
evaluations is presented in Table 2. 
7.2.2 
Special Assays or Procedures 
Immunogenicity 
Assays to determine serum levels of HAI and Neut antibodies will be performed at Southern 
Research. Immunogenicity testing will include performing HAI and Neut antibody assays 
against the 2017 H7N9 vaccine virus on serum samples collected for Group 1 on Days 1 
(baseline), 22, and 43, and at approximately 180 days post second 2017 H7N9 IIV dose (Day 
202), and for Group 2 on Days 22 (baseline), 43, and 64, and at approximately 180 days post 
second 2017 H7N9 IIV dose (Day 223). Serological antibody assays will be performed 
against the vaccine viruses in IIV4 from serum samples collected at baseline (Day 1) and 
approximately 21 and 180 days following receipt of IIV4 (Groups 1, 2 and 3).  Subjects who 
withdraw early will have HAI and Neut antibody assays run on available sera.  
The assays for determination of the NA content and antibodies to the NA are under 
development. If successful, the correlation of NA content in the 2017 H7N9 IIV with elicited 
N9 NA-specific serum antibody responses may be assessed.  2017 H7N9 IIV and adjuvant 
will be shipped from the DMID CMS to the NA content assay designated laboratory for NA 
content assessment. Any laboratory involved with the determination of NA content or NA-
specific antibody responses will remain blinded to the HAI and Neut antibodies results 
performed at Southern Research. 
After all subjects in Groups 1 and 2 have completed the Day 64 clinic visit (Visit 08 for 
Group 1 and Visit 10 for Group 2), samples for the HAI and Neut analysis will be shipped 
from the DMID CMS to Southern Research. Following the last subject’s clinic visit at 180 
days after the last study vaccination (Visit 10 for Group 1 and Visit 12 for Group 2), samples 
for the final HAI and Neut analysis will be shipped from the DMID CMS to Southern 
Research.  
For all Groups, serological antibody assays will be performed against the vaccine viruses in 
IIV4 from serum samples collected at baseline (Study Day 1), and 21 and 180 days following 
receipt of IIV4.  
Venous blood samples (10 mL) will also be collected for future use at the same time points. 
Sites may elect to allow subjects to consent to study participation but to have the option to 


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opt out of the collection of the future use samples, or may include collection of future use 
samples as a condition of study participation and not allow the opt out option. 
The volume of venous blood to be collected for immunogenicity assays and future research is 
presented in Table 2. 
 
 


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Table 2 a 
Group 1 Venipuncture Volumes (mL): 
Vaccination Period 
Study Visit Number 
V00 
V01 
V03 
V04 
V06 
 
V07 
Total 
(mL) 
Study Day post Dose 1 
(H7N9 + IIV4) 
Screening 
(Optional)  
D -28 to -1 
Enrollment 
Dose 1 
D1 
 D8+2d 
 D22+7d 
 D29 
 
 D43 
Study Day post Dose 2 
(H7N9) 
 
 
 
Dose 2 
D1 
 D8+2d 
 
 D22+7d 
Study Vaccination 
 
X 
 
X 
 
 
 
ESR 
4^ 
4^* 
 
 
 
 
4  
Clinical Baseline and 
Safety Laboratory 
Evaluations~ 
  
10† 
10 
10† 
10 
 
40  
Immunogenicity Assays 
  
10† 
 
10† 
 
10 
30 
Serum Sample for Future 
Research# 
 
10† 
10 
10† 
10 
10 
50 
Total (mL) 
(4) 0 
(30) 34 
20 
30 
20 
 
20 
 
124 
^ Drawn up to 28 days prior to study vaccination. Results must be known and confirmed to meet the eligibility 
criterion prior to randomization and first study vaccination.   
~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr. 
# Sites may elect to allow subjects to consent to study participation but to have the option to opt out of the 
collection of the future use samples, or may include collection of future use samples as a condition of study 
participation and not allow the opt out option.† 
All blood drawn immediately prior to study vaccination. 
* Not required if done at the optional screening visit 
 
 
 
 
 
 


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Group 1 Venipuncture Volumes (mL): 
Follow-up Period 
Study Visit Number 
V08 
V09 
V10 
Total 
(mL) 
Study Day post Dose 1 
(H7N9 + IIV4) 
D64 
D181 
±14 
D202 
Study Day post Dose 2 
(H7N9) 
D43+7 
 
D181±14 
Clinical Safety Laboratory 
Evaluations~ 
 
 
 
 
Immunogenicity Assays 
 
10 
10 
20 
Serum Sample for Future 
Research# 
10 
10 
10 
30 
Total (mL) 
10 
20 
20 
50 
^  Drawn up to 28 days prior to study vaccination. Results must be known and confirmed to meet the eligibility 
criterion prior to randomization and first study vaccination.   
~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr. 
# Sites may elect to allow subjects to consent to study participation but to have the option to opt out of the 
collection of the future use samples, or may include collection of future use samples as a condition of study 
participation and not allow the opt out option. 
† All blood drawn immediately prior to study vaccination. 
*  Not required if done at the optional screening visit 
 


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Table 2 b 
Group 2 Venipuncture Volumes (mL): 
Vaccination Period 
Study Visit Number 
V00 
V01 
V03 
V04 
V06 
 
V07 
Total 
(mL) 
Study Day post Dose 1 
(IIV4) 
Screening 
(Optional)  
D -28 to -1 
Enrollment 
and Dose 1 
D1 
D8+2d 
D22+7d 
D29 
D43 
Study Day post Dose 2 
(H7N9) 
 
 
 
Dose 2 
D1 
D8+2d 
D22+7d 
Study Day post Dose 3 
(H7N9) 
 
 
 
 
 
 Dose 3 
D1 
 
Study Vaccination 
 
X 
 
X 
 
X 
 
ESR 
4^ 
4^* 
 
 
 
 
4  
Clinical Baseline and 
Safety Laboratory 
Evaluations~ 
  
10† 
10 
10† 
 
10 
10† 
50  
Immunogenicity Assays 
  
10† 
 
10† 
 
10† 
30 
Serum Sample for Future 
Research# 
 
10† 
10 
10† 
10 
10† 
50 
Total (mL) 
(4) 0 
(30) 34 
20 
30 
20 
 
30 
 
134 
^ Drawn up to 28 days prior to study vaccination. Results must be known and confirmed to meet the eligibility 
criterion prior to randomization and first study vaccination.   
~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr. 
# Sites may elect to allow subjects to consent to study participation but to have the option to opt out of the 
collection of the future use samples, or may include collection of future use samples as a condition of study 
participation and not allow the opt out option. 
† All blood drawn immediately prior to study vaccination. 
*  Not required if done at the optional screening visit 


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Group 2 Venipuncture Volumes (mL): 
Follow-up Period 
Study Visit Number 
 
V09 
V10 
V11 
V12 
Total 
(mL) 
Study Day post Dose 1 
(IIV4) 
 
D50 
D64 
D181 
±14 
D223 
Study Day post Dose 2 
(H7N9) 
 
D29 
D43 
 
D202 
Study Day post Dose 3 
(H7N9) 
 
D8+2d 
D22+7d 
 
D181±14 
 
Clinical Safety Laboratory 
Evaluations~ 
 
10  
 
 
 
10  
Immunogenicity Assays 
 
 
10 
10 
10 
30 
Serum Sample for Future 
Research# 
 
10 
10 
10 
10 
40 
Total (mL) 
20 
20 
20 
20 
80 
~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr. 
# Sites may elect to allow subjects to consent to study participation but to have the option to opt out of the 
collection of the future use samples, or may include collection of future use samples as a condition of study 
participation and not allow the opt out option.


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Table 2 c 
Group 3 Venipuncture Volumes (mL): 
Vaccination and Follow-up  
Study Visit Number 
V00 
V01 
V03 
V04 
V05 
V06 
V07 
Total 
(mL) 
Study Day post Dose 1 
(IIV4) 
Screening 
(Optional)  
D -28 to -1 
Enrollment 
and Dose 1 
D1 
D8+2d 
D22+7d 
D43+7d 
D64+7d 
D181±14 d 
Study Vaccination 
 
X 
 
 
 
 
 
 
ESR 
4^ 
4^* 
 
 
 
 
 
4  
Clinical Baseline and 
Safety Laboratory 
Evaluations~ 
  
10† 
10 
 
 
 
 
20  
Immunogenicity Assays 
  
10† 
 
10 
 
 
10 
30 
Serum Sample for Future 
Research# 
 
10† 
10 
10 
10 
10 
10 
60 
Total (mL) 
(4) 0 
(30) 34 
20 
20 
10 
10 
20 
114 
^ Drawn up to 28 days prior to study vaccination. Results must be known and confirmed to meet the eligibility 
criterion prior to randomization and first study vaccination.   
~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr. 
# Sites may elect to allow subjects to consent to study participation but to have the option to opt out of the 
collection of the future use samples, or may include collection of future use samples as a condition of study 
participation and not allow the opt out option. 
† All blood drawn immediately prior to study vaccination. 
*  Not required if done at the optional screening visit 
7.2.3 
Specimen Preparation, Handling, and Shipping 
7.2.3.1 
Instructions for Specimen Preparation, Handling, and Storage 
Instructions for specimen preparation, handling, and storage are included in the central (clinical) 
laboratory manual and protocol-specific MOP as appropriate. 
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 


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storage temperature and documentation as detailed in the central (clinical) laboratory manual and 
protocol-specific MOP as appropriate. 
Specimens for safety laboratory evaluations will be shipped from the participating VTEU sites to 
the central (clinical) laboratory. 
Specimens for HAI and Neut antibody assays will be shipped from the participating VTEU sites 
to the DMID CMS, and then provided by the DMID CMS to Southern Research in a blinded 
manner. 
Specimens for the NA antibody assays will be shipped from the participating VTEU sites to the 
DMID CMS, and then provided by the DMID CMS to the NA antibody assay laboratory once it 
has been identified. 
Further instructions for specimen shipment are included in the central (clinical) laboratory 
manual and protocol-specific MOP, as appropriate. 


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8 
STUDY SCHEDULE 
Complete study schedule details listed by type of visit are described below. Refer also to 
Sections 4 and 7 and Appendix A: Schedule of Study Procedures and Evaluations. For detailed 
information regarding the study schedule for discontinued subjects, please reference the MOP– 
Discontinued Subjects Remaining on Study. 
8.1 
Screening (Optional) and Enrollment Visits, All Groups 
8.1.1 
Visit 00, Screening Clinic Visit (Optional) (Day -28 to -1) 
• Subjects will be provided with a description of this trial (purpose and study procedures) 
and asked to read and sign the ICF. The ICF will be signed prior to performing any study 
procedures, including administration of the first and second study vaccinations for Group 
1, and the first study vaccination for Groups 2 and 3. 
• Demographic information will be obtained by interview of subjects. 
• Eligibility criteria will be reviewed with subjects. 
• Complete medical history will be obtained by interview of subjects to ensure eligibility. 
• All concomitant medications taken within 60 days prior to signing the 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 the 
first study vaccination.  
• Subject receipt of licensed seasonal influenza vaccine over the previous two seasons, 
what type (inactivated or live attenuated), and approximate date of vaccination will be 
recorded on the appropriate DCF, if known. Prior receipt of licensed seasonal influenza 
vaccine in the 2017/2018 season is exclusionary (see Section 5.1.2).  
• Subject receipt of non-seasonal influenza vaccines, including those that are experimental, 
what type (inactivated or live attenuated), what subtype (e.g., A/H3, A/H5, A/H9) and 
approximate date of vaccination will be recorded on the appropriate DCF, if known. Prior 
receipt of non-seasonal influenza vaccines are not exclusionary, except influenza A/H7 
vaccines (see Section 5.1.2). 
• Vital signs, including oral temperature, pulse, and blood pressure, will be obtained to 
ensure eligibility prior to first study vaccination. Subjects must not eat or drink anything 
hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
• 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, abdomen, general appearance, musculoskeletal and nervous system and as 
assessment for signs suggestive of a PIMMC, by a study clinician licensed to make 
medical diagnoses and listed on the Form FDA 1572 as the site principal investigator or 
sub-investigator. 
• A urine or serum pregnancy test may be performed on all women of childbearing 
potential. Results must be negative to ensure eligibility. 
• Approximately 4 mL of venous blood will be collected for ESR, and performed locally 
by the site. The ESR value must be confirmed as less than 30 mm per hour prior to 
randomization and the first vaccination. 
8.1.2 
Visit 01, Day 1, Enrollment (for subjects previously screened at Day -28 to -1) 
and Dose 1, Clinic Visit 
Group 1 (First and Second Study Vaccinations):  AS03 adjuvanted 2017 H7N9 IIV + IIV4 
Groups 2 and 3 (First Study Vaccination):  IIV4 
• Subject’s willingness to participate will be reconfirmed and documented in the subject’s 
study records prior to performing any further study procedures, including administration 
of the first vaccination. 
• Eligibility criteria, including results of the ESR will be reviewed.  
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects prior to the vaccination and any changes since the previous clinic visit or contact 
will be noted. 
• All concomitant medications will be reviewed with subjects prior to the first vaccination 
for accuracy and completeness. Any new concomitant medications taken since the 
screening visit will be reviewed with subjects and assessed for continued eligibility prior 
to the first vaccination.  
• Vital signs, including oral temperature, pulse, and blood pressure, will be obtained to 
ensure eligibility prior to the first vaccination. Vital signs assessed on Day 1 prior to the 
first 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 the first vaccination, if indicated based on review of 
complete medical history and any updates obtained by interview of subjects since the 


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screening visit, by a study clinician licensed to make medical diagnoses and listed on the 
Form FDA 1572 as the site principal investigator or sub-investigator. 
• A urine or serum pregnancy test will be performed within 24 hours prior to the first 
vaccination on all women of childbearing potential. Results must be negative and known 
prior to randomization and first vaccination. 
• Subjects will be enrolled in AdvantageEDCSM and assigned randomly to a treatment arm 
prior to the first vaccination. 
• Pre-administration reactogenicity assessments will be performed prior to the first 
vaccination to establish baseline.  
• Approximately 10 mL of venous blood will be collected immediately prior to the first 
vaccination for baseline serum antibody assays. 
• Approximately 10 mL of venous blood will be collected immediately prior to the first 
vaccination for baseline clinical safety labs (WBC, Hgb, PLT, ALT, T. Bili, Cr), and 
performed by the central (clinical) laboratory. The results from this blood draw will not 
be available or reviewed prior to the vaccination, and will serve as a safety baseline 
assessment only. 
• Approximately 10 mL of venous blood will be collected prior to vaccination for future 
research from subjects who consent, either by signing an informed consent form that 
includes collection of future use samples as a condition of study participation or by 
indicating that they opt in to sample collection for future use if the informed consent form 
allows the option to choose that option. 
• Subjects will then receive a single dose of vaccine (Group 1 will receive 2 vaccines) via 
IM injection into the deltoid muscle of the preferred arm, or if randomized to Group 1, in 
both arms within 15 minutes of each other. The site of injection (right and/or left arm) 
and time of administration will be recorded on the appropriate DCF. Subjects will be 
observed in the clinic for at least 20 minutes after the vaccination. The 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, any unsolicited 
AEs, and concomitant medications. Subjects will be encouraged to take their oral 
temperature around the same time each day. Subjects must not eat or drink anything hot 
or cold, or smoke within 10 minutes prior to taking oral temperature. Subjects will be 
instructed on how to use their memory aid and how to measure and record AEs prior to 
discharge from the clinic. Subjects will be instructed to notify the study center if they 
develop any severe reactions after the vaccination(s). If the site principal investigator or 


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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 Dose 1, Clinic Visit 
Group 1 (First and Second Study Vaccinations):  AS03 adjuvanted 2017 H7N9 IIV + IIV4 
Groups 2 and 3 (First Study Vaccination):  IIV4 
• 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 the first vaccination. 
• Demographic information will be obtained by interview of subjects. 
• Complete medical history will be obtained by interview of subjects prior to the first 
vaccination to ensure eligibility. 
• All concomitant medications taken within 60 days prior to signing the ICF will be 
reviewed with subjects and reported in the eCRF prior to the first vaccination. 
Medications reported in the eCRF are limited to those taken within 30 days prior to the 
first vaccination. 
• Subject receipt of licensed seasonal influenza vaccine over the previous two seasons, 
what type (inactivated or live attenuated), and approximate date of vaccination will be 
recorded on the appropriate DCF, if known. Prior receipt of 2017-2018 licensed seasonal 
influenza vaccine is exclusionary.  
• Subject receipt of non-seasonal influenza vaccines, including those that are experimental, 
what type (inactivated or live attenuated), what subtype (e.g., A/H3, A/H5, A/H9) and 
approximate date of vaccination will be recorded on the appropriate DCF, if known. Prior 
receipt of non-seasonal influenza vaccines are not exclusionary, except influenza A/H7 
vaccines (see Section 5.1.2). 
• Vital signs, including oral temperature, pulse, and blood pressure, will be obtained to 
ensure eligibility prior to the first vaccination. Vital signs assessed on Day 1 prior to the 
first 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 the first vaccination for the calculation of 
BMI. 
• A physical examination will be performed on all subjects to include the following organs 
and organ systems: skin, head and neck, lungs, heart, liver, spleen, extremities, lymph 


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nodes, abdomen, general appearance, musculoskeletal and nervous system and as 
assessment for signs suggestive of a PIMMC, by a study clinician licensed to make 
medical diagnoses and listed on the Form FDA 1572 as the site principal investigator or 
sub-investigator. 
• Approximately 4 mL of venous blood will be collected for ESR, and performed locally 
by the site. The ESR value must be confirmed as less than 30 mm per hour prior to 
randomization and first vaccination. 
• Eligibility criteria, including results of ESR evaluation, will be reviewed with subjects 
prior to the first vaccination to ensure continued eligibility. 
• A urine or serum pregnancy test will be performed within 24 hours prior to the first 
vaccination on all women of childbearing potential. Results must be negative and known 
prior to randomization and first vaccination. 
• Subjects will be enrolled in AdvantageEDCSM and assigned randomly to a treatment arm 
prior to the first vaccination. 
• Pre-administration reactogenicity assessments will be performed prior to the first 
vaccination to establish baseline.  
• Approximately 10 mL of venous blood will be collected immediately prior to the first 
vaccination for baseline serum antibody assays. 
• Approximately 10 mL of venous blood will be collected immediately prior to the first 
vaccination for baseline clinical safety labs (WBC, Hgb, PLT, ALT, T. Bili, Cr), and 
performed by the central (clinical) laboratory. The results from this blood draw will not 
be available or reviewed prior to vaccination, and will serve as a safety baseline 
assessment only. 
• Approximately 10 mL of venous blood will be collected prior to vaccination for future 
research from subjects who consent, either by signing an informed consent form that 
includes collection of future use samples as a condition of study participation or by 
indicating that they opt in to sample collection for future use if the informed consent form 
allows the option to choose that option. 
• Subjects will then receive a single dose of study vaccine (Group 1 will receive 2 
vaccines) via IM injection into the deltoid muscle of the preferred arm, or if randomized 
to Group 1, in both arms within 15 minutes of each other. The site of injection (right 
and/or left arm) and time of administration will be recorded on the appropriate DCF. 
Subjects will be observed in the clinic for at least 20 minutes after the vaccination. The 
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, any unsolicited 
AEs, and concomitant medications. Subjects will be encouraged to take their oral 
temperature around the same time each day. Subjects must not eat or drink anything hot 
or cold, or smoke within 10 minutes prior to taking oral temperature. Subjects will be 
instructed on how to use their memory aid and how to measure and record AEs prior to 
discharge from the clinic. Subjects will be instructed to notify the study center if they 
develop any severe reactions after the vaccination(s). If the site principal investigator or 
appropriate sub-investigator deems the reaction severe enough, further instructions will 
be given to the subject on the proper course of action, including a return to the clinic for 
immediate evaluation if appropriate. 
8.2 
Follow-up Visits, Group 1 
Follow-up visits are scheduled in reference to vaccination dates as indicated for each visit 
window. 
8.2.1 
Visit 02, Day 4, Memory Aid Review, Phone Call 
(Window: 3 (±1) days post Dose 1) 
Study personnel will contact subjects by phone to solicit any AE/SAE and concomitant 
medication information (including solicitation for receipt of any non-study influenza vaccines, 
including those that are experimental, what type (inactivated or live attenuated), what subtype 
(e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be recorded on the 
appropriate DCF, if known and not previously collected) and review information on their 
memory aid. Based on the information, subjects may be asked to return to the clinic for 
evaluation. 
8.2.2 
Visit 03, Day 8, Clinic Visit 
(Window: 7 (+2) days post first Dose 1)) 
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects and any changes since the previous clinic visit or contact will be noted. 
• Memory aid information will be reviewed with subjects. 
• All concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 


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recorded on the appropriate DCF, if known and not previously collected) 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 principal investigator or sub-investigator. 
• The H7N9 and IIV4 vaccination sites will be examined. 
• Approximately 10 mL of venous blood will be collected for safety labs, WBC, Hgb, PLT, 
ALT, T. Bili, Cr, and performed by the central (clinical) laboratory. 
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent, either by signing an informed consent form that includes collection of 
future use samples as a condition of study participation or by indicating that they opt in to 
sample collection for future use if the informed consent form allows the option to choose 
that option. 
8.2.3 
Visit 04, Day 22, Dose 2, Clinic Visit 
(Window: 21 (+7) days post Dose 1) 
• Eligibility criteria will be reviewed with subjects prior to the vaccination to ensure 
continued eligibility. 
• For a subject to receive the vaccination, refer to section 5.2.3 for subsequent dose 
eligibility criteria.   
• Interim medical history, including an assessment for new medical conditions stability of 
chronic diseases and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects prior to the vaccination and any changes since the previous clinic visit or contact 
will be noted. 
• All concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected. Prior receipt of 
non-seasonal influenza vaccines are not exclusionary, except influenza A/H7 vaccines 
(see Section 5.1.2) will be recorded on the appropriate DCF prior to the vaccination. 
• All AE/SAEs will be recorded on the appropriate DCF.  


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• Vital signs, including oral temperature, pulse, and blood pressure, will be obtained prior 
to the study vaccination. Subjects must not eat or drink anything hot or cold, or smoke 
within 10 minutes prior to taking oral temperature. Note: Vital signs are not required for 
subjects who are discontinued from receipt of the vaccination and are being followed for 
safety. 
• A targeted physical examination, including an assessment for signs suggestive of 
PIMMCs, may be performed prior to the vaccination, if indicated based on review of 
interim medical history, by a study clinician licensed to make medical diagnoses and 
listed on the Form FDA 1572 as the site principal investigator or sub-investigator. 
• A urine or serum pregnancy test will be performed within 24 hours prior to the study 
vaccination on all women of childbearing potential. Results must be negative and known 
prior to the vaccination. 
• Pre-administration reactogenicity assessments will be performed prior to the study 
vaccination to establish baseline.  
• Approximately 10 mL of venous blood will be collected immediately prior to the 
vaccination for safety labs WBC, Hgb, PLT, ALT, T. Bili, Cr, and performed by the 
central (clinical) laboratory. 
• Approximately 10 mL of venous blood will be collected immediately prior to the 
vaccination for serum antibody assays. 
• Approximately 10 mL of venous blood will be collected immediately prior to the 
vaccination for future research from subjects who consent, either by signing an informed 
consent form that includes collection of future use samples as a condition of study 
participation or by indicating that they opt in to sample collection for future use if the 
informed consent form allows the option to choose that option. 
• Subjects will then receive a single dose of study vaccine via IM injection into the deltoid 
muscle of the preferred arm.  If the subject has no preference, the second dose of 
adjuvanted 2017 H7N9 IIV may be given in either arm as long as there is no hindrance of 
the reactogenicity assessment. The site of injection (right or left arm) and time of 
administration will be recorded on the appropriate DCF. Subjects will be observed in the 
clinic for at least 20 minutes after the vaccination. The 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, any unsolicited 
AEs, and concomitant medications. Subjects will be encouraged to take their oral 
temperature around the same time each day. Subjects must not eat or drink anything hot 


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or cold, or smoke within 10 minutes prior to taking oral temperature. Subjects will be 
instructed on how to use their memory aid and how to measure and record AEs prior to 
discharge from the clinic. Subjects will be instructed to notify the study center if they 
develop any severe reactions after the vaccination. If the site principal investigator or 
appropriate sub-investigator deems the reaction severe enough, further instructions will 
be given to the subject on the proper course of action, including a return to the clinic for 
immediate evaluation if appropriate. 
8.2.4 
Visit 05, Day 25, Memory Aid Review, Phone Call 
(Window: 3 (±1) days post Dose 2)  
Study personnel will contact subjects by phone to solicit any AE/SAE and concomitant 
medication information (including solicitation for receipt of any non-study influenza vaccines, 
including those that are experimental, what type (inactivated or live attenuated), what subtype 
(e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be recorded on the 
appropriate DCF, if known and not previously collected) and review information on their 
memory aid. Based on the information, subjects may be asked to return to the clinic for 
evaluation. Note: For subjects who are discontinued from the receipt of Dose 2, AEs will be 
limited to SAEs and MAAEs, including NOCMCs and PIMMCs. 
8.2.5 
Visit 06, Day 29, Clinic Visit 
(Window: 7 (+2) days post Dose 2) 
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects and any changes since the previous clinic visit or contact will be noted. 
• Memory aid information will be reviewed with subjects. 
• All concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected) will be recorded 
on the appropriate DCF. 
• All AE/SAEs will be recorded on the appropriate DCF. Note: for subjects who 
discontinued from the receipt of Dose 2, AEs will be limited to SAEs and MAAEs, 
including NOCMCs and PIMMCs. 
• A targeted physical examination, including an assessment for signs suggestive of 
PIMMCs, may be performed, if indicated based on review of interim medical history, by 


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a study clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as 
the site principal investigator or sub-investigator. 
• The Dose 2 (third vaccination) site will be examined. 
• Approximately 10 mL of venous blood will be collected for safety labs WBC, Hgb, PLT, 
ALT, T. Bili, Cr, and performed by the central (clinical) laboratory. 
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent, either by signing an informed consent form that includes collection of 
future use samples as a condition of study participation or by indicating that they opt in to 
sample collection for future use if the informed consent form allows the option to choose 
that option. 
8.2.6 
Visit 07, Day 43, Safety Follow-up Clinic Visit 
(Window: 21 (+7) days post Dose 2) 
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects and any changes since the previous clinic visit or contact will be noted. 
• All concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected) will be recorded 
on the appropriate 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 principal investigator or sub-investigator. 
• Approximately 10 mL of venous blood will be collected for serum antibody assays. 
• Approximately 10 mL of venous blood will be for future research from subjects who 
consent, either by signing an informed consent form that includes collection of future use 
samples as a condition of study participation or by indicating that they opt in to sample 
collection for future use if the informed consent form allows the option to choose that 
option. 


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8.2.7 
Visit 08, Day 64, Safety Follow-up, Clinic Visit 
(Window: 42 days (+7) days post Dose 2) 
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects and any changes since the previous clinic visit or contact will be noted. 
• Concomitant medications (solicitation only for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected) will be recorded 
on the appropriate DCF. 
• All SAEs and MAAEs, including NOCMs and PIMMCs, 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 principal investigator or sub-investigator.  
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent to collection of serum for future research. 
8.2.8 
Visit 09, Day 181, Safety Follow-up, Clinic Visit  
(Window: 180 (±14) days post Dose 1)  
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic medical diseases, and symptoms suggestive of PIMMCs, will be obtained by 
interview of subjects and any changes since the previous clinic visit or contact will be 
noted. 
• Concomitant medications (solicitation only for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected) will be recorded 
on the appropriate DCF. 
• AEs limited to MAAEs, including NOCMCs and PIMMCs, and SAEs that have occurred 
since the previous clinic visit or contact will be solicited  


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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 principal investigator or sub-investigator. 
• Approximately 10 mL of venous blood will be collected for serum antibody assays.  
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent, either by signing an informed consent form that includes collection of 
future use samples as a condition of study participation or by indicating that they opt in to 
sample collection for future use if the informed consent form allows the option to choose 
that option.  
8.2.9 
Visit 10, Day 202, Safety Follow-up, Clinic Visit 
(Window: 180 (±14) days post Dose 2) 
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic medical diseases, and symptoms suggestive of PIMMCs, will be obtained by 
interview of subjects and any changes since the previous clinic visit or contact will be 
noted. 
• Concomitant medications (solicitation only for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected) will be recorded 
on the appropriate DCF.AEs limited to MAAEs, including NOCMCs and PIMMCs, and 
SAEs that have occurred since the previous clinic visit or contact will be solicited  
• A targeted physical examination, including an assessment for signs suggestive of 
PIMMCs, may be performed, if indicated based on review of interim medical history, by 
a study clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as 
the site principal investigator or sub-investigator. 
• Approximately 10 mL of venous blood will be collected for serum antibody assays.  
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent, either by signing an informed consent form that includes collection of 
future use samples as a condition of study participation or by indicating that they opt in to 
sample collection for future use if the informed consent form allows the option to choose 
that option.  


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8.2.10 
Visit 11, Day 387, Safety Follow-up, Phone Call 
(Window: 365 (±14) days post Dose 2) 
Subjects will be contacted by phone to query for safety events. AEs limited to MAAEs, 
including NOCMCs and PIMMCS, and SAEs that have occurred since the previous clinic visit 
or contact will be solicited. Based on the information, subjects may be asked to return to the 
clinic for evaluation. 
8.3 
Follow-up Visits, Group 2  
Follow-up visits are scheduled in reference to vaccination dates as indicated for each visit 
window. 
8.3.1 
Visit 02, Day 4, Memory Aid Review, Phone Call 
(Window: 3 (±1) days post Dose 1) 
Study personnel will contact subjects by phone to solicit any AE/SAE and concomitant 
medication information (including solicitation for receipt of any non-study influenza vaccines, 
including those that are experimental, what type (inactivated or live attenuated), what subtype 
(e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be recorded on the 
appropriate DCF, if known and not previously collected) and review information on their 
memory aid. Based on the information, subjects may be asked to return to the clinic for 
evaluation. 
8.3.2 
Visit 03, Day 8, Clinic Visit 
(Window: 7 (+2) days post Dose 1)  
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects and any changes since the previous clinic visit or contact will be noted. 
• Memory aid information will be reviewed with subjects. 
• All concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected) will be recorded 
on the appropriate DCF. 
• All AE/SAEs will be recorded on the appropriate DCF.  


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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 principal investigator or sub-investigator. 
• The first vaccination site will be examined. 
• Approximately 10 mL of venous blood will be collected for safety labs, WBC, Hgb, PLT, 
ALT, T. Bili, Cr, and performed by the central (clinical) laboratory. 
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent, either by signing an informed consent form that includes collection of 
future use samples as a condition of study participation or by indicating that they opt in to 
sample collection for future use if the informed consent form allows the option to choose 
that option. 
8.3.3 
Visit 04, Day 22, Dose 2, Clinic Visit 
(Window: 21 (+7) days post first study vaccination)  
• Eligibility criteria will be reviewed with subjects prior to the vaccination to ensure 
continued eligibility. 
• For a subject to receive the vaccination, refer to section 5.2.3 for subsequent dose 
eligibility criteria.   
• Interim medical history, including an assessment for new medical conditions stability of 
chronic diseases and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects prior to the vaccination and any changes since the previous clinic visit or contact 
will be noted. 
• All concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected. Prior receipt of 
non-seasonal influenza vaccines are not exclusionary, except influenza A/H7 vaccines 
(see Section 5.1.2) will be recorded on the appropriate DCF prior to the vaccination. 
• All AE/SAEs will be recorded on the appropriate DCF.  
• Vital signs, including oral temperature, pulse, and blood pressure, will be obtained prior 
to the vaccination. Subjects must not eat or drink anything hot or cold, or smoke within 


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10 minutes prior to taking oral temperature. Note: Vital signs are not required for subjects 
who are discontinued from receipt of Dose 2 and are being followed for safety. 
• A targeted physical examination, including an assessment for signs suggestive of 
PIMMCs, may be performed prior to the vaccination, if indicated based on review of 
interim medical history, by a study clinician licensed to make medical diagnoses and 
listed on the Form FDA 1572 as the site principal investigator or sub-investigator. 
• A urine or serum pregnancy test will be performed within 24 hours prior to the 
vaccination on all women of childbearing potential. Results must be negative and known 
prior to the vaccination. 
• Pre-administration reactogenicity assessments will be performed prior to the vaccination 
to establish baseline.  
• Approximately 10 mL of venous blood will be collected immediately prior to the 
vaccination for safety labs WBC, Hgb, PLT, ALT, T. Bili, Cr, and performed by the 
central (clinical) laboratory. 
• Approximately 10 mL of venous blood will be collected immediately prior to the 
vaccination for serum antibody assays. 
• Approximately 10 mL of venous blood will be collected immediately prior to the 
vaccination for future research from subjects who consent, either by signing an informed 
consent form that includes collection of future use samples as a condition of study 
participation or by indicating that they opt in to sample collection for future use if the 
informed consent form allows the option to choose that option. 
• Subjects will then receive a single dose of study vaccine via IM injection into the deltoid 
muscle of the preferred arm. The second vaccination may be given in either arm as long 
as there is no interference with the reactogenicity assessment. The site of injection (right 
or left arm) and time of administration will be recorded on the appropriate DCF. Subjects 
will be observed in the clinic for at least 20 minutes after the vaccination. The 
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, any unsolicited 
AEs, and concomitant medications. Subjects will be encouraged to take their oral 
temperature around the same time each day. Subjects must not eat or drink anything hot 


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or cold, or smoke within 10 minutes prior to taking oral temperature. Subjects will be 
instructed on how to use their memory aid and how to measure and record AEs prior to 
discharge from the clinic. Subjects will be instructed to notify the study center if they 
develop any severe reactions after the second vaccination. If the site principal 
investigator or appropriate sub-investigator deems the reaction severe enough, further 
instructions will be given to the subject on the proper course of action, including a return 
to the clinic for immediate evaluation if appropriate. 
8.3.4 
Visit 05, Day 25, Memory Aid Review, Phone Call 
(Window: 3 (±1) days post Dose 2) 
Study personnel will contact subjects by phone to solicit any AE/SAE and concomitant 
medication information (including solicitation for receipt of any non-study influenza vaccines, 
including those that are experimental, what type (inactivated or live attenuated), what subtype 
(e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be recorded on the 
appropriate DCF, if known and not previously collected) and review information on their 
memory aid. Based on the information, subjects may be asked to return to the clinic for 
evaluation. Note: For subjects who are discontinued from the receipt of Dose 2, AEs will be 
limited to SAEs and MAAEs, including NOCMCs and PIMMCs. 
8.3.5 
Visit 06, Day 29, Clinic Visit 
(Window: 7 (+2) days post Dose 2) 
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects and any changes since the previous clinic visit or contact will be noted. 
• Memory aid information will be reviewed with subjects. 
• All concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected) will be recorded 
on the appropriate DCF. 
• All AE/SAEs will be recorded on the appropriate DCF. Note: for subjects who 
discontinued from the receipt of Dose 2, AEs will be limited to SAEs and MAAEs, 
including NOCMCs and PIMMCs. 


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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 principal investigator or sub-investigator. 
• The second vaccination site will be examined. 
• Approximately 10 mL of venous blood will be collected for safety labs WBC, Hgb, PLT, 
ALT, T. Bili, Cr, and performed by the central (clinical) laboratory. 
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent, either by signing an informed consent form that includes collection of 
future use samples as a condition of study participation or by indicating that they opt in to 
sample collection for future use if the informed consent form allows the option to choose 
that option. 
8.3.6 
Visit 07, Day 43, Dose 3, Clinic Visit 
(Window: 21 (+7) days post Dose 2) 
• Eligibility criteria will be reviewed with subjects prior to the vaccination to ensure 
continued eligibility. 
• For a subject to receive the third vaccination, refer to section 5.2.3 for subsequent dose 
eligibility criteria.  
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects and any changes since the previous clinic visit or contact will be noted. 
• All concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected. Prior receipt of 
non-seasonal influenza vaccines are not exclusionary, except influenza A/H7 vaccines 
(see Section 5.1.2) will be recorded on the appropriate DCF. 
• Vital signs, including oral temperature, pulse, and blood pressure, will be obtained prior 
to the vaccination. Subjects must not eat or drink anything hot or cold, or smoke within 
10 minutes prior to taking oral temperature. Note: Vital signs are not required for subjects 
who are discontinued from receipt of Dose 3 and are being followed for safety. 


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• All AE/SAEs will be recorded on the appropriate DCF. Note: Vital signs are not required 
for subjects who are discontinued from receipt of Dose 3 and are being followed for 
safety. 
• A targeted physical examination, including an assessment for signs suggestive of 
PIMMCs, may be performed, if indicated based on review of interim medical history, by 
a study clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as 
the site principal investigator or sub-investigator. 
• A urine or serum pregnancy test will be performed within 24 hours prior to the 
vaccination on all women of childbearing potential. Results must be negative and known 
prior to the vaccination. 
• Pre-administration reactogenicity assessments will be performed prior to the vaccination 
to establish baseline.  
• Approximately 10 mL of venous blood will be collected immediately prior to the 
vaccination for safety labs WBC, Hgb, PLT, ALT, T. Bili, Cr, and performed by the 
central (clinical) laboratory.   
• Approximately 10 mL of venous blood will be collected immediately prior to the 
vaccination for serum antibody assays. 
• Approximately 10 mL of venous blood will be collected immediately prior to the 
vaccination for future research from subjects who consent, either by signing an informed 
consent form that includes collection of future use samples as a condition of study 
participation or by indicating that they opt in to sample collection for future use if the 
informed consent form allows the option to choose that option. 
• Subjects will then receive a single dose of study vaccine via IM injection into the deltoid 
muscle of the preferred arm. The third vaccination may be given in either arm as long as 
there is no interference with the reactogenicity assessment. The site of injection (right or 
left arm) and time of administration will be recorded on the appropriate DCF. Subjects 
will be observed in the clinic for at least 20 minutes after the vaccination. The third 
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, any unsolicited 
AEs, and concomitant medications. Subjects will be encouraged to take their oral 


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temperature around the same time each day. Subjects must not eat or drink anything hot 
or cold, or smoke within 10 minutes prior to taking oral temperature. Subjects will be 
instructed on how to use their memory aid and how to measure and record AEs prior to 
discharge from the clinic. Subjects will be instructed to notify the study center if they 
develop any severe reactions after the vaccination. If the site principal investigator or 
appropriate sub-investigator deems the reaction severe enough, further instructions will 
be given to the subject on the proper course of action, including a return to the clinic for 
immediate evaluation if appropriate. 
8.3.7 
Visit 08, Day 46, Memory Aid Review, Phone Call 
(Window: 3 (±1) days post Dose 3) 
Study personnel will contact subjects by phone to solicit any AE/SAE and concomitant 
medication information (including solicitation for receipt of any non-study influenza vaccines, 
including those that are experimental, what type (inactivated or live attenuated), what subtype 
(e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be recorded on the 
appropriate DCF, if known and not previously collected) and review information on their 
memory aid. Based on the information, subjects may be asked to return to the clinic for 
evaluation. Note: For subjects who are discontinued from the receipt of Dose 3, AEs will be 
limited to SAEs and MAAEs, including NOCMCs and PIMMCs. 
8.3.8 
Visit 09, Day 50, Clinic Visit 
(Window: 7 (+2) days post Dose 3) 
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects and any changes since the previous clinic visit or contact will be noted. 
• Memory aid information will be reviewed with subjects. 
• All concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected) will be recorded 
on the appropriate DCF. 
• All AE/SAEs will be recorded on the appropriate DCF. Note: for subjects who 
discontinued from the receipt of Dose 3, AEs will be limited to SAEs and MAAEs, 
including NOCMCs and PIMMCs. 


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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 principal investigator or sub-investigator. 
• The third vaccination site will be examined. 
• Approximately 10 mL of venous blood will be collected for safety labs, WBC, Hgb, PLT, 
ALT, T. Bili, Cr, and performed by the central (clinical) laboratory. 
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent, either by signing an informed consent form that includes collection of 
future use samples as a condition of study participation or by indicating that they opt in to 
sample collection for future use if the informed consent form allows the option to choose 
that option. 
8.3.9 
Visit 10, Day 64, Safety Follow-up, Clinic Visit 
(Window: 21 (+7) days post Dose 3) 
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects and any changes since the previous clinic visit or contact will be noted. 
• All concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected) will be recorded 
on the appropriate DCF. 
• All AE/SAEs will be recorded on the appropriate DCF. Note: for subjects who 
discontinued from the receipt of Dose 3, AEs will be limited to SAEs and MAAEs, 
including NOCMCs and PIMMCs. 
• A targeted physical examination, including an assessment for signs suggestive of 
PIMMCs, may be performed, if indicated based on review of interim medical history, by 
a study clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as 
the site principal investigator or sub-investigator.  
• Approximately 10 mL of venous blood will be collected for serum antibody assays. 
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent, either by signing an informed consent form that includes collection of 


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future use samples as a condition of study participation or by indicating that they opt in to 
sample collection for future use if the informed consent form allows the option to choose 
that option. 
8.3.10 
Visit 11, Day 181, Safety Follow-up, Clinic Visit  
   
(Window: 180 (±14) days post Dose 1) 
 
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic medical diseases, and symptoms suggestive of PIMMCs, will be obtained by 
interview of subjects and any changes since the previous clinic visit or contact will be 
noted. 
• Concomitant medications (solicitation only for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected) will be recorded 
on the appropriate DCF. 
• AEs limited to MAAEs including NOCMCs, PIMMCs, and SAEs that have occurred 
since the previous clinic visit or contact will be solicited.  
• A targeted physical examination, including an assessment for signs suggestive of 
PIMMCs, may be performed, if indicated based on review of interim medical history, by 
a study clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as 
the site principal investigator or sub-investigator. 
• Approximately 10 mL of venous blood will be collected for serum antibody assays. 
   
• Approximately 10 mL of venous blood will be collected for future research, either by 
signing an informed consent form that includes collection of future use samples as a 
condition of study participation or by indicating that they opt in to sample collection for 
future use if the informed consent form allows the option to choose that option.  
8.3.11 
Visit 12, Day 223, Safety Follow-up, Clinic Visit 
(Window: 180 (±14) days post Dose 3) 
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic medical diseases, and symptoms suggestive of PIMMCs, will be obtained by 


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interview of subjects and any changes since the previous clinic visit or contact will be 
noted. 
• Concomitant medications (solicitation only for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected) will be recorded 
on the appropriate DCF. 
• AEs limited to MAAEs including NOCMCs, PIMMCs, and SAEs that have occurred 
since the previous clinic visit or contact will be solicited.  
• A targeted physical examination, including an assessment for signs suggestive of 
PIMMCs, may be performed, if indicated based on review of interim medical history, by 
a study clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as 
the site principal investigator or sub-investigator. 
• Approximately 10 mL of venous blood will be collected for serum antibody assays. 
   
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent, either by signing an informed consent form that includes collection of 
future use samples as a condition of study participation or by indicating that they opt in to 
sample collection for future use if the informed consent form allows the option to choose 
that option.  
8.3.12 
Visit 13, Day 408, Safety Follow-up, Phone Call 
(Window: 365 (±14) days post Dose 3) 
Subjects will be contacted by phone to query for safety events. AEs limited to MAAEs, 
including NOCMCs and PIMMCS, and SAEs that have occurred since the previous clinic visit 
or contact will be solicited. Based on the information, subjects may be asked to return to the 
clinic for evaluation. 
8.4 
Follow-up Visits, Group 3 
Follow-up visits are scheduled in reference to the vaccination date that is indicated for each visit 
window. 
8.4.1 
Visit 02, Day 4, Memory Aid Review, Phone Call 
(Window: 3 (±1) days post dose) 


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Study personnel will contact subjects by phone to solicit any AE/SAE and concomitant 
medication information (including solicitation for receipt of any non-study influenza vaccines, 
including those that are experimental, what type (inactivated or live attenuated), what subtype 
(e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be recorded on the 
appropriate DCF, if known and not previously collected) and review information on their 
memory aid. Based on the information, subjects may be asked to return to the clinic for 
evaluation. 
8.4.2 
Visit 03, Day 8, Clinic Visit 
(Window: 7 (+2) days post dose)  
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects and any changes since the previous clinic visit or contact will be noted. 
• Memory aid information will be reviewed with subjects. 
• All concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected) will be recorded 
on the appropriate 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 principal investigator or sub-investigator. 
• The vaccination site will be examined. 
• Approximately 10 mL of venous blood will be collected for safety labs, WBC, Hgb, PLT, 
ALT, T. Bili, Cr, and performed by the central (clinical) laboratory. 
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent, either by signing an informed consent form that includes collection of 
future use samples as a condition of study participation or by indicating that they opt in to 
sample collection for future use if the informed consent form allows the option to choose 
that option. 


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8.4.3 
Visit 04, Day 22, Safety Follow-up, Clinic Visit 
(Window: 21 (+7) days post dose)  
• Interim medical history, including an assessment for new medical conditions stability of 
chronic diseases and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects and any changes since the previous clinic visit or contact will be noted. 
• All concomitant medications (including solicitation for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected) will be recorded 
on the appropriate 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 principal investigator or sub-investigator. 
• Approximately 10 mL of venous blood will be collected for serum antibody assays. 
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent, either by signing an informed consent form that includes collection of 
future use samples as a condition of study participation or by indicating that they opt in to 
sample collection for future use if the informed consent form allows the option to choose 
that option. 
8.4.4 
Visit 05, Day 43, Safety Follow-up, Clinic Visit 
(Window: 42 (+7) days post dose) 
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects and any changes since the previous clinic visit or contact will be noted. 
• Concomitant medications (solicitation only for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected) will be recorded 
on the appropriate DCF. 


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• All SAEs and MAAEs, including NOCMs and PIMMCs, 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 principal investigator or sub-investigator. 
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent, either by signing an informed consent form that includes collection of 
future use samples as a condition of study participation or by indicating that they opt in to 
sample collection for future use if the informed consent form allows the option to choose 
that option. 
 
8.4.5 
Visit 06, Day 64, Safety Follow-up, Clinic Visit 
(Window: 63 (+7) days post dose) 
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects and any changes since the previous clinic visit or contact will be noted. 
• Concomitant medications (solicitation only for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected) will be recorded 
on the appropriate DCF.  
• All SAEs and MAAEs, including NOCMs and PIMMCs, 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 principal investigator or sub-investigator.  
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent, either by signing an informed consent form that includes collection of 
future use samples as a condition of study participation or by indicating that they opt in to 
sample collection for future use if the informed consent form allows the option to choose 
that option. 
8.4.6 
Visit 07, Day 181, Safety Follow-up, Clinic Visit 
(Window: 180 (±14) days post dose) 
 


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• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects and any changes since the previous clinic visit or contact will be noted. 
• Concomitant medications (solicitation only for receipt of any non-study influenza 
vaccines, including those that are experimental, what type (inactivated or live attenuated), 
what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected) will be recorded 
on the appropriate DCF. 
• All SAEs and MAAEs, including NOCMs and PIMMCs, 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 principal investigator or sub-investigator.  
• Approximately 10 mL of venous blood will be collected for serum antibody assays. 
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent, either by signing an informed consent form that includes collection of 
future use samples as a condition of study participation or by indicating that they opt in to 
sample collection for future use if the informed consent form allows the option to choose 
that option. 
8.4.7 
Visit 08, Day 366, Safety Follow-up, Phone Call 
(Window: 365 (±14) days post dose) 
Subjects will be contacted by phone to query for safety events. AEs limited to MAAEs, 
including NOCMCs, and PIMMCS, and SAEs that have occurred since the previous clinic visit 
or contact will be solicited. Based on the information, subjects may be asked to return to the 
clinic for evaluation. 
8.5 
Early Termination Visit (if needed) 
The following activities will be performed at the early termination visit on subjects who 
withdraw, are withdrawn, or terminated from this trial: 
• Interim medical history, including an assessment for new medical conditions and 
symptoms suggestive of PIMMCs, will be obtained by interview of subjects and any 
changes since the previous clinic visit or contact will be noted. 


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• Memory aid information will be reviewed with subjects (if within 7 days after the last 
study vaccination). 
• All concomitant medications will be recorded on the appropriate DCF (if within 21 days 
after the last study vaccination). Receipt of any non-study influenza vaccine, including 
those that are experimental, what type (inactivated or live attenuated), what subtype (e.g., 
A/H3, A/H5, A/H9) and approximate date of vaccination will be recorded on the 
appropriate DCF, if known and not previously collected, will be recorded if within 180 
days after the last vaccination. 
• All AE/SAEs will be recorded on the appropriate DCF. AEs will be limited to SAEs and 
MAAEs, including NOCMCs and PIMMCs, that have occurred since the previous clinic 
visit or contact will be solicited (if after 21 days after the last vaccination).  
• Vital signs, including oral temperature, pulse, and blood pressure, may be obtained if 
indicated. Subjects must not eat or drink anything hot or cold, or smoke within 10 
minutes prior to taking oral temperature. 
• A targeted physical examination, including an assessment for signs suggestive of 
PIMMCs, may be performed, if indicated based on review of interim medical history, by 
a study clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as 
the site principal investigator or sub-investigator. 
• The study vaccination site(s) will be examined (if within 7 days after the last 
vaccination). 
• Post-administration reactogenicity assessments will be performed (if within 7 days after 
the last vaccination). 
• Approximately 10 mL of venous blood will be collected for WBC, Hgb, PLT, ALT, T. 
Bili, Cr, and performed by the central (clinical) laboratory (if within 7 days after the last 
vaccination). 
• Approximately 10 mL of venous blood will be collected for serum antibody assays (if 
within 21 days after the last vaccination). 
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent (if within 21 days after the last vaccination).  


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8.6 
Unscheduled Visit (if needed) 
Unscheduled visits may occur at any time during this trial. Any of the following activities may 
be performed: 
• Interim medical history, including an assessment for new medical conditions and 
symptoms suggestive of PIMMCs, will be obtained by interview of subjects and any 
changes since the previous clinic visit or contact will be noted (if indicated). 
• Memory aid information will be reviewed with subjects (if within 7 days after the last 
vaccination). 
• All concomitant medications will be recorded on the appropriate DCF (if within 21 days 
after the last vaccination). Receipt of any non-study influenza vaccine, including those 
that are experimental, what type (inactivated or live attenuated), what subtype (e.g., 
A/H3, A/H5, A/H9) and approximate date of vaccination will be recorded on the 
appropriate DCF, if known and not previously collected, will be recorded if within 180 
days after the last vaccination. 
• All AE/SAEs will be recorded on the appropriate DCF. AEs will be limited to SAEs and 
MAAEs, including NOCMCs and PIMMCs, if after 21 days after the last vaccination. 
• Vital signs, including oral temperature, pulse, and blood pressure, may be obtained if 
indicated. Subjects must not eat or drink anything hot or cold, or smoke within 10 
minutes prior to taking oral temperature. 
• A targeted physical examination, including an assessment for signs suggestive of 
PIMMCs, may be performed, if indicated based on review of interim medical history, by 
a study clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as 
the site principal investigator or sub-investigator. 
• The study vaccination site(s) will be examined (if within 7 days after the last 
vaccination). 
• Post-administration reactogenicity assessments will be performed (if within 7 days after 
the last vaccination). 
• Approximately 10 mL of venous blood will be collected for WBC, Hgb, PLT, ALT, T. 
Bili, Cr, and performed by the central (clinical) laboratory (if indicated). 
• Approximately 10 mL of venous blood will be collected for serum antibody assays (if 
within 21 days after the last vaccination). 


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• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent (if within 21 days after the last 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 the first study vaccination through approximately 12 
months after the last study vaccination. 
2. Solicited AEs – reactogenicity events occurring from the time of each study vaccination 
through 7 days after each study vaccination: 
a) Injection site reactions including pruritus, ecchymosis, erythema, induration 
(hardness)/edema (swelling), pain, and tenderness. 
b) Systemic reactions including fever, feverishness, fatigue, malaise, myalgia, arthralgia, 
headache, and nausea. 
3. Clinical safety laboratory AEs occurring from the time of each study vaccination through 
approximately 7 days after each study vaccination. Parameters to be evaluated include 
WBC, Hgb, PLT, ALT, T. Bili, Cr. 
4. Unsolicited AEs – non-serious AEs occurring from the time of each study vaccination 
through approximately 21 days after each study vaccination. 
5. MAAEs, including NOCMCs and PIMMCs, occurring from the time of the first study 
vaccination through approximately 12 months after the last study vaccination. 
9.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety 
Parameters 
9.2.1 
Adverse Events 
Adverse Event (AE): (ICH) E6 defines an AE as any untoward medical occurrence in a patient 
or clinical investigation subject administered a pharmaceutical product regardless of its causal 
relationship to the study treatment. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a medicinal (investigational) product. The occurrence of an AE may come to the attention 
of study personnel during study visits and interviews of a study recipient presenting for medical 
care, or upon review by a study monitor. 


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


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• 
Mild (Grade 1): Events require minimal or no treatment and do not interfere with the 
subject’s daily activities. 
• 
Moderate (Grade 2): Events result in a low level of inconvenience or concern with 
therapeutic measures. Moderate events may cause some interference with functioning and 
daily activities. 
• 
Severe (Grade 3): Events interrupt the subject’s daily activities and may require systemic 
drug therapy or other treatment. Severe events are usually incapacitating. 
Relationship to Study Product: The licensed study clinician’s assessment of an AE's 
relationship to study product is part of the documentation process, but it is not a factor in 
determining what is or is not reported in this trial. If there is any doubt as to whether a clinical 
observation is an AE, the event should be reported. The relationship to study product must be 
assessed for AEs using the terms: related or not related. In a clinical trial, the study product must 
always be suspect. To help assess, the following guidelines are used: 
• Related – There is a reasonable possibility that the study product caused the AE. 
Reasonable possibility means that there is evidence to suggest a causal relationship 
between the study product and the AE. 
• Not Related – There is not a reasonable possibility that the administration of the study 
product caused the event. 
9.2.2 
Reactogenicity 
Reactogenicity events are AEs that are common and known to occur following administration of 
this type of study vaccine. The following Toxicity Grading Scales will be used to grade solicited 
local (injection site) and systemic (subjective and quantitative) reactions: 
Injection Site Reactogenicity Grading 
Injection Site Reaction 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Pain – experienced 
without touching the 
injection site 
(spontaneous discomfort) 
Subject is aware of pain, 
but it does not interfere 
with daily activity, and 
no pain medication is 
taken 
Subject is aware of pain; 
there is interference with 
daily activity or it 
requires repeated use of a 
non-narcotic pain reliever 
for >24 hours 
Subject is aware of pain, 
and it prevents daily 
activity or requires any use 
of a narcotic pain reliever 
Tenderness – hurts only 
when injection site is 
The area immediately 
surrounding the injection 
The area immediately 
surrounding the injection 
The area immediately 
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Injection Site Reaction 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
touched or the arm is 
moved 
site hurts only when 
touched or with arm 
motion, and it does not 
interfere with daily 
activity 
site hurts when touched or 
with arm motion, and it 
interferes with daily 
activity 
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: 
Local (Injection Site) Reactogenicity Measurements 
Local (Injection Site) Reaction 
Small 
Medium 
Large 
Ecchymosis (Bruising)* 
<20 mm 
20 mm – 50 mm 
>50 mm 
Erythema (Redness)* 
<20 mm 
20 mm – 50 mm 
>50 mm 
Induration (Hardness)/Edema 
(Swelling)* 
<20 mm 
20 mm – 50 mm 
>50 mm 
* Will not be used as halting criteria. 
Subjective Systemic Reactogenicity Grading 
Systemic (Subjective) 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Feverishness 
(Chills/Shivering/Sweating) 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 


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


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


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


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Clinical safety laboratory results# will be graded as follows: 
Clinical Safety Laboratory Adverse Event Grading
75 
Hematology 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
WBC 103/µL (Decrease) 
2.5 – 3.9 
1.5 – 2.4 
<1.5 
WBC 103/µL (Increase) 
10.6 – 15.0 
15.1 – 20.0 
>20.0 
Hgb g/dL (Decrease) (Female) 
10.1 – 11.4 
8.5 – 10 
<8.5 
Hgb g/dL (Decrease) (Male) 
11.0 – 12.4 
9.5 – 10.9 
<9.5 
Platelets 103/µL (Decrease) 
125 – 139 
100 – 124 
<100 
Platelets 103/µL (Increase) 
416 – 550 
551– 750 
>750 
 
 
 
 
Chemistry 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
ALT IU/L (Increase) (Female) 
44 – 100 
101 – 200 
>200 
ALT IU/L (Increase) (Male) 
61 – 138 
139 – 275 
>275 
Total Bilirubin mg/dL (Increase) – 
when accompanied by any increase in 
ALT 
1.30 – 1.59 
1.60 – 1.80 
>1.80 
Total Bilirubin mg/dL (Increase) – 
when ALT is normal 
1.30 – 1.89 
1.90 – 2.40 
>2.40 
Creatinine mg/dL (Increase) 
(Female) 
1.1 – 1.7 
1.8 – 2.0 
>2.0 
Creatinine mg/dL (Increase) (Male) 
1.4 – 1.7 
1.8 – 2.0 
>2.0 
# Clinical laboratory evaluations assessed on Day 1 prior to the first study vaccination will be considered as 
baseline. 
9.2.4 Serious Adverse Events 
Serious Adverse Event (SAE): An AE or suspected adverse reaction is considered “serious” if, 
in the view of either the site principal investigator or sponsor, it results in any of the following 
outcomes: 
• Death, 
• A life-threatening AE*, 
• Inpatient hospitalization or prolongation of existing hospitalization, 


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• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions, or 
• A congenital anomaly/birth defect. 
• Important medical events that may not result in death, be life-threatening, or require 
hospitalizations may be considered serious when, based upon appropriate medical 
judgment they may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse. 
* Life-threatening AE. An AE is considered “life-threatening” if, in the view of either the site 
principal investigator or sponsor, its occurrence places the patient or subject at immediate risk of 
death. It does not include an AE that, had it occurred in a more severe form, might have caused 
death. 
SAEs will be: 
• 
Assessed for severity and relationship to study product and alternate etiology (if not 
related to study product) by a licensed study physician listed on the Form FDA 1572 as 
the site principal investigator or sub-investigator. 
• 
Recorded on the appropriate SAE form and eCRF. 
• 
Followed through resolution by a licensed study physician listed on the Form FDA 1572 
as the site principal investigator or sub-investigator. 
• 
Reviewed and evaluated by an Independent Safety Monitor (ISM) (as deemed necessary), 
the DSMB (periodic review unless related), DMID, and the IRB. 
9.2.5 
Procedures to be Followed in the Event of Abnormal Laboratory Test Values or 
Abnormal Clinical Findings 
The site principal investigator or appropriate sub-investigator is responsible for recording all 
AE/SAEs that are observed or reported during this trial, regardless of the relationship to study 
product. AE/SAEs, abnormal laboratory test values, or abnormal clinical findings will be 
collected, assessed, documented, reported, and followed appropriately, using a local laboratory 
as necessary. In determining eligibility, refer to section 5.1 and the protocol-specific MOP. 
 
 


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9.3 
Reporting Procedures 
Solicited injection site and systemic reactogenicity events will be documented and reported from 
the time of each study vaccination through 7 days after each study vaccination. 
Clinical safety laboratory AEs will be documented and reported from the time of each study 
vaccination through approximately 7 days after each study vaccination. 
Unsolicited non-serious AEs will be documented and reported from the time of each study 
vaccination through approximately 21 days after each study vaccination. 
SAEs and MAAEs, including NOCMCs and PIMMCs, will be documented and reported from 
the time of the first study vaccination through approximately 12 months after the last study 
vaccination. 
9.3.1 
Serious Adverse Events 
Any AE that meets a protocol-defined serious criterion must be submitted immediately (within 
24 hours of site awareness) on an SAE form to the DMID Pharmacovigilance Group at the 
following address: 
DMID Pharmacovigilance Group 
Clinical Research Operations and Management Support (CROMS) 
6500 Rock Spring Dr. Suite 650 
Bethesda, MD 20817, USA 
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 study subject safety and protocol conduct. 


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


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SAEs and MAAEs, including NOCMCs and PIMMCs, will be collected, assessed, and followed 
from the time of the first study vaccination through resolution even if this extends beyond the 
trial-reporting period (approximately 12 months after the last study vaccination). 
Resolution of an AE/SAE is defined as the return to pretreatment status or stabilization of the 
condition with the expectation that it will remain chronic. 
Follow-up procedures, evaluations, and outcomes will be recorded on the appropriate DCF. 
9.5 
Halting Rules 
For the purpose of halting rules only events that occur following the administration of the AS03 
adjuvanted 2017 H7N9 will be considered. Further enrollment and study vaccinations will be 
halted for DSMB review/recommendation if any of the following are reported: 
• Any subject experiences ulceration, abscess, or necrosis at the injection site related to 
study product administration. 
• Any 2 or more subjects experience laryngospasm, bronchospasm, or anaphylaxis within 1 
day after administration of study product that is considered related to study product. 
• Three or more subjects experience generalized urticaria (defined as occurring at more 
than two body parts) within 3 days after administration of study product that is 
considered related to study product. 
• Any subject experiences an SAE from the time of the first 2017 H7N9  vaccination 
through 14 days after each 2017 H7N9 vaccination. 
• 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 through the 
subject’s last study visit. 
This trial will also be halted for DSMB review/recommendation if, within 7 days after 
administration of any study vaccination, any of the following occurs within the 2017 A/H7N9 
IIV AS03-adjuvanted treatment arms (Group 1 or Group 2).   
• 7% or more of subjects (with a minimum of 3 subjects) who received at least one dose of 
study vaccine to date, cumulative to all 2017 H7N9 vaccine administrations, across 
Groups 1 and 2, 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.  


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• 7% or more of subjects (with a minimum of 3 subjects) who received at least one dose of 
study vaccine to date, cumulative to all 2017 H7N9 vaccine administration, across 
Groups 1 and 2, experience the same severe (Grade 3) study vaccine-related subjective 
systemic reaction, for which the severity (grade) is corroborated by study personnel. 
• 7% or more of subjects (with a minimum of 3 subjects) who received at least one dose of 
study vaccine to date, cumulative to all 2017 H7N9 vaccine administration, across 
Groups 1 and 2, experience the same severe (Grade 3) study vaccine-related quantitative 
systemic reaction. 
• 7% or more of subjects (with a minimum of 3 subjects) who received at least one dose of 
study vaccine to date, cumulative to all 2017 H7N9 vaccine administration, across 
Groups 1 and 2, experience the same severe (Grade 3) study vaccine-related clinical 
safety laboratory AE. 
Grading scales for solicited injection site and systemic (subjective and quantitative) reactions are 
included in Section 9.2.2. 
Grading scales for clinical safety laboratory AEs are included in Section 9.2.3. 
If any of the halting rules are met following any subject receipt of any study vaccination, then 
this trial will not continue with the remaining enrollments or study vaccinations without a review 
by and recommendation from the DSMB to proceed. 
DMID retains the authority to suspend additional enrollment and study interventions/ 
administration of study product during the entire trial, as applicable. 
The DMID Medical Monitor is empowered to stop enrollment and study vaccinations if AEs that 
meet the halting criteria are reported. 
9.6 
Safety Oversight 
9.6.1 
Independent Safety Monitor (ISM) 
The ISM is a physician with relevant expertise whose primary responsibility is to provide 
independent safety monitoring in a timely fashion. For this trial, an ISM is not required. 
However, at each participating VTEU site, and at the request of DMID, in real time, the principal 
investigator should be able to identify an independent physician to function as an ad hoc ISM. 
That person should have the privileges to examine the subject, review the subject’s medical and 
study records, and provide an independent medical assessment and recommendation to DMID. 


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9.6.2 
Data and Safety Monitoring Board (DSMB) 
Safety oversight will be conducted by a DSMB that is an independent group of experts that 
monitors subject safety and advises DMID. The DSMB members will be separate and 
independent of study personnel participating in this trial and should not have scientific, financial 
or other conflict of interest related to this trial. The DSMB will consist of members with 
appropriate expertise to contribute to the interpretation of the data from this trial. The DSMB 
will operate under the rules of a DMID-approved charter that will be written at the organizational 
meeting of the DSMB. Procedures for DSMB reviews/meetings will be defined in the charter. 
Reports may include enrollment and demographic information, medical history, concomitant 
medications, physical assessments, clinical laboratory values, dosing compliance, 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 review study progress and participant, clinical, safety, and reactogenicity data at 
the following time points: 
• Data review for safety at study specific time frames; at least annually. 
• Electronic review when 8-day reactogenicity and clinical safety laboratory data following 
the first study vaccination is available for 25% of study participants. 
• Approximately when 8-day reactogenicity and clinical safety laboratory data following 
the first study vaccination is available for 75% of study participants. 
• Final review meeting: 6 to 8 months after clinical database lock to review the cumulative 
unblinded safety and immunogenicity data for this trial.  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. 
• Ad hoc when a halting rule is met, for immediate concerns regarding observations during 
this trial, or as needed. 
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, including expected and observed rates of the expected AEs. The 
DSMB will review grouped 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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The DSMB will operate under the rules of a DMID-approved charter that will be written at the 
organizational meeting of the DSMB. At this time, each data element that the DSMB needs to 
assess will be clearly defined. Procedures for DSMB reviews/meetings will be defined in the 
charter. The DSMB will review applicable data to include, but not limited to, study progress and 
participant, clinical, safety and reactogenicity data. Reports may include enrollment and 
demographic information, medical history, concomitant medications, physical assessments, 
clinical laboratory values, dosing compliance, solicited and unsolicited AE/SAEs, and HAI and 
Neut antibody assay results. 
DMID or the DSMB chair may convene the DSMB on an ad hoc basis according to protocol 
criteria or if there are immediate concerns regarding observations during the course of this trial. 
The DMID Medical Monitor is empowered to stop enrollment and study vaccinations if AEs that 
meet the halting criteria are reported. The DMID Medical Monitor and the ISM (as deemed 
necessary) will be responsible for reviewing SAEs in real time. The DSMB will review SAEs on 
a regular basis and ad hoc during this trial. 


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


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11 
STATISTICAL CONSIDERATIONS 
11.1 
Introduction 
The goal of this clinical trial is to assess, in healthy adults ages 19 – 64, the safety, 
reactogenicity, and immunogenicity of a pre-pandemic AS03-adjuvanted 2017 H7N9 IIV when 
two doses are administered 21 days apart either sequentially or simultaneously (within 15 
minutes) with licensed seasonal influenza vaccine. Primary immunogenicity objectives include 
evaluating interference with response to 2017 H7N9 IIV vaccine virus strain 21 days post dose 2, 
and evaluating interference with response to seasonal influenza virus strains 21 days post receipt 
of IIV4. 
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 when 2017 
H7N9 IIV is administered sequentially or simultaneously (within 15 minutes) with licensed 
seasonal influenza vaccine, and to uncover any safety issues that occur at a sufficiently high rate 
that they might be observed in a study of this size. The sample size facilitates formal testing of 
selected hypotheses as discussed in Section 11.4.3, along with the probability of observing safety 
outcomes and the precision of immunogenicity outcomes. 
11.3 
Study Outcome Measures 
Please refer to study outcome measures in Section 3.2. 
11.4 
Sample Size Considerations 
Please refer to study design outlined in Section 4.0. 
11.4.1 
Study Population 
The study population for this clinical trial includes males and non-pregnant females, 19-64 years 
of age, who are in good health and meet all eligibility criteria. The subjects will be recruited 
from the general population at the participating VTEU sites that have substantial experience 
conducting large influenza vaccine studies. 


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11.4.2 
Subject Enrollment and Follow-up 
Based on the accrual rates observed in similar studies, it seems reasonable to expect that the 
participating VTEUs will be able to enroll this trial in a timely fashion. In previous DMID trials 
of A/H7N9 vaccines, 5 VTEUs recruited 975 healthy adults, ages 19-64 in 10 weeks. Prior 
experience suggests up to 15% of subjects may be excluded from the per protocol analysis for 
post dose 3 assessments, either because they did not receive the second or third study 
vaccinations, were lost-to-follow-up, or because they had a protocol deviation requiring their 
exclusion from the per protocol analysis.  
A total of N=60 in Groups 1-2, and N = 30 in Group 3 will be enrolled and randomized. 
Assuming up to 15% drop out by Day 64, this will ensure at least N=50 in Groups 1-2 and N=25 
in Group 3 are available for the primary immunogenicity 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 the last study 
vaccination. The second segment consists of a 6-month immunogenicity assessment and follow-
up safety assessments through approximately 12 months after the last study vaccination. 
11.4.3 
Sample Size 
This study is planned to enroll a minimum of 60 subjects in Groups 1-2, and 30 subjects in 
Group 3. This 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 and to uncover any 
safety issues that occur at a sufficiently high rate that they might be observed in a study of this 
size. As such, the type one error rate, alpha = 0.05, is not adjusted for multiple comparisons.  
While this study is not designed to test any specific null hypothesis, the following tables 
illustrate the precision and power for select estimates and comparisons of interest. 
Table 3 indicates the probability of observing one or more safety events, such as solicited 
injection site or systemic reactogenicity events or an unsolicited non-serious AE of a particular 
type for a single treatment arm (N = 30 or 60), and for all subjects receiving AS03-adjuvanted 
2017 H7N9 IIV (N = 120). 
Table 3: Power (%) to Detect Safety Events: 
Event 
Frequency 
N = 30 
N = 60 
N = 120 
≥10% 
Very Common 
96 
>99 
>99 
≥1% 
26 
45 
70 


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Common 
≥0.1% 
Uncommon 
3 
6 
11 
≥0.01% 
Rare 
<1 
<1 
1 
Binomial confidence intervals (CI) are widest (have the least precision) when the response rate is 
50%. Table 4 is presented to indicate the worst-case scenario for precision of observed exact 
(Clopper-Pearson) binomial confidence intervals. 
Table 4: Precision of Binomial Confidence Intervals: 
N 
95% CI 
30 
31-69 
60 
37-63 
120 
40-60 
 
For each of the primary immunogenicity objective, a power analysis is provided below for 
testing the following hypotheses with the planned sample size, where pc = proportion responders 
in comparator arm; pe = proportion responders in experimental arm. 
Test for difference in proportion responders: 
H0: pc – pe = 0 – No difference in proportion responders 
H1: pc – pe ≠ 0 – difference in response rates 
 
Table 5 and Table 6 present the minimum detectable differences in the proportion of subjects 
responding (e.g., attaining seroconversion or a titer ≥1:40) between two treatment arms using a 
two-sided Likelihood Ratio Test and alpha = 0.05. 
 
Primary Immunogenicity Objective 1: Evaluate antibody responses against A/H7N9 at 
approximately 21 days following receipt of two doses of AS03-adjuvanted 2017 H7N9 IIV. 
Comparison between simultaneous and sequential receipt to IIV4, i.e., Group 1 at Day 43 vs. 
Group 2 at Day 64. 
 
Table 5: Objective 1 -Minimum Detectable Difference in Proportion Responders with 80% 
Power (N = 50 per group) 
Assumed Proportion Responders  
comparator arm (pc) 
Minimum detectable 
difference in response 
rate (pc – pe) 
0.50 
0.27 


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Assumed Proportion Responders  
comparator arm (pc) 
Minimum detectable 
difference in response 
rate (pc – pe) 
0.60 
0.27 
0.70 
0.27 
0.80 
0.26 
0.90 
0.22 
 
Primary Immunogenicity Objective 2: Evaluate antibody responses against the seasonal 
influenza strains at approximately 21 days following receipt of IIV4. 
Comparator Group (N = 75):   
• Group 2 (IIV4/H7N9/H7N9) + Group 3 (IIV4) at Day 22  
Experimental Groups (N = 50/group): 
• Group 1 (H7N9+IIV4/H7N9) at Day 64 
 
Table 6: Objective 2 - Minimum Detectable Difference in Proportion Responders with 80% 
Power 
Assumed  
Proportion Responders  
comparator arm (pc) 
Minimum detectable 
decrease in response rate 
(pc - pe) 
0.40 
0.23 
0.50 
0.24 
0.60 
0.25 
0.70 
0.25 
0.80 
0.23 
0.90 
0.20 
11.5 
Planned Interim Analyses 
Interim analyses will only be used to terminate this trial in the event that unanticipated safety 
events deemed to be of sufficient concern require such action by the sponsor. These assessments 
will not be made on the basis of testing a formal statistical hypothesis; therefore, p-value 
adjustment will not be made to any analyses. A DSMB will be convened by DMID to review 
study progress and participant, clinical, safety, reactogenicity and immunogenicity data as 
described in Section 9.6.2. 


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No interim analysis of immunogenicity is planned, however, a preliminary report of safety and 
immunogenicity data through Day 64 will be prepared as described in Section 11.6; though this 
report will be released while subjects remain in the trial for long-term safety and immunogenicity 
follow-up, it will be considered the final analysis of these data. 
Emergent public health needs may dictate additional interim safety, reactogenicity, and/or 
immunogenicity analyses be performed on available information at any time during the trial. If 
this occurs, immunogenicity data will be analyzed as results are available from the central 
immunogenicity laboratory. 
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, including expected and 
observed rates of the expected AEs. The DSMB will review grouped 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. 
Additionally, this trial will be monitored to determine if any of the halting rules described in 
Section 9.5 are met. 
11.5.2 
Interim Immunogenicity Review 
No interim immunogenicity analysis is planned. Should emergent public health needs dictate 
immunogenicity review, immune responses will be summarized in terms of strain-specific 2017 
A/H7N9 and IIV4 HAI and Neut antibody titers for subjects that receive sequential or 
simultaneous administration of AS03-adjuvanted 2017 H7N9 IIV and seasonal IIV4. It is 
anticipated that all analyses will be carried out in parallel for both assays, but reports may be 
prepared separately for HAI and Neuts if results are available on different timelines. Interim 
analyses will focus on rates of titers ≥1:40, seroconversion (defined as either a pre-vaccination 
titer <1:10 and a post-vaccination titer ≥1:40 or a pre-vaccination titer ≥1:10 and a minimum 
four-fold rise in post-vaccination titer) and 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. 


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Any immunogenicity reports would be provided by the SDCC to the DMID Scientific Lead and 
Clinical Project manager, and the DSMB. Reports will include data summarized by treatment 
arm. 
11.6 
Final Analysis Plan 
Clinical, safety, and reactogenicity data through approximately 21 days after the third study 
vaccination will represent the primary clinical database for this trial. Once the last subject 
completes the visit that occurs approximately 21 days after the third study vaccination, the 
primary clinical database will be cleaned, monitored, and locked. Analyses of safety, 
reactogenicity, and available immunogenicity (HAI and Neut antibody assays through Day 64) 
data by treatment arm are planned. A preliminary report will be prepared by the SDCC after the 
primary clinical database is locked and all HAI and Neut data for the 2017 H7N9 vaccine strain 
and all IIV4 strains are received through 21 days after the last study vaccination is received. 
These analyses may be made available to the sponsor for planning subsequent trials and to the 
lead principal investigator for publication. These analyses will not be used to make any decisions 
concerning the conduct of this trial. All analyses of data included in the preliminary report for 
early release will be considered the final analysis of these data, and also included in the final 
clinical study report (CSR). 
Analysis of exploratory immunogenicity endpoints 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. 
A formal statistical analysis plan (SAP) will be developed and finalized prior the primary clinical 
database lock, which defines the analyses to be included in the Preliminary report, and the final 
CSR. 
11.6.1 
Analysis Populations 
The Safety Analysis population includes all subjects who received at least one dose of study 
vaccine. 
The modified intent-to-treat (mITT) population includes all subjects who received at least one 
dose of study vaccine and contributed both pre- and at least one post-study vaccination venous 
blood samples for immunogenicity testing (HAI or Neut antibody assays) for which valid results 


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were reported. For analyses using the mITT population, subjects in Group 2 who discontinue 
treatment after receiving the single IIV4 dose (Dose 1) but prior to receiving the first dose of the 
H7N9 vaccine (Dose 2) will be analyzed with group 3. All other subjects will be grouped based 
on randomized treatment arm.  
The per protocol (PP) population includes all subjects in the mITT subset with the following 
exclusions: 
• Data from all available visits for subjects found to be ineligible at baseline. 
• Data from all visits subsequent to major protocol deviations, such as: 
• Second or third study vaccination not received, 
• Second or third study vaccination received out of window, 
• Receipt of non-study licensed live vaccine within 30 days before or after each study 
vaccination, 
• Receipt of non-study licensed inactivated vaccine within 14 days before or after 
each study vaccination, 
• Receipt of immunosuppressive therapy (e.g., corticosteroids) within 30 days before 
or after each study vaccination. 
• Data from any visit that occurs substantially out of window. 
For analyses using the PP population, subjects will be grouped based on study vaccinations 
received. 
11.6.2 
Safety Data 
Summaries and analysis of safety data will be presented for the Safety Analysis Population. All 
summaries and analyses will be presented for all subjects. 
Solicited AEs will be summarized by severity for each day after each study vaccination (Days 1-
8 post each study vaccination) and as the maximum severity over all 8 days. Additionally, 
solicited AEs will be analyzed by taking the most severe response over the follow-up period, 
dichotomizing into a binary variable (none versus mild, moderate, or severe) and using standard 
techniques, such as exact confidence intervals, to summarize the proportion of subjects reporting 
each symptom, any injection site symptom, and any systemic symptom. Summaries of solicited 
AEs will be presented separately for each study vaccination as well as overall study vaccinations 
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treatment arms using Chi-square or Fisher’s exact test. The proportion of subjects reporting 
solicited symptoms between the different study vaccinations (i.e., first vs. second, first vs. third, 
second vs. third, as applicable within each study group) will be compared using McNemar’s test. 
Unsolicited AEs will be coded by Medical Dictionary for Regulatory Activities (MedDRA) for 
preferred term and system organ class (SOC). The numbers of SAEs 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 preferred term and SOC, relevant dates (study 
vaccinations and AEs), severity, relatedness, and outcome for each event. Non-serious 
unsolicited AEs will be summarized as number and percentage of subjects reporting at least one 
event in each MedDRA preferred term and SOC, cross tabulated by severity and relationship to 
study product. Additionally, the proportion of subjects and exact 95% 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 2017 H7N9 or IIV4 strain-specific 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 <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 influenza vaccine(s), and these 
covariates may be considered statistical modeling. As an exploratory analysis, models may be 
developed to evaluate the relationship between study vaccination schedule and immune response.  
Additionally, N1, N2 and N9 NA-specific antibody assays are in development.  If successful, 
N1, N2 and N9 NA-specific responses may be assessed at baseline, 21, 42, 63, and 180 days 
after receipt of the first study vaccination.  For each time point, summaries may include number 


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and percentage of subjects with detectable N1, N2 and N9 NA response (to be defined in SAP 
based following assay development and selection) and GMTs along with corresponding 95% 
CIs. Descriptive summary statistics will be provided for all assays and time points. The 
correlation of N1, N2 and N9 NA response with HAI and Neut antibody titers will be evaluated, 
and plots such as reverse cumulative distributions or longitudinal presentations of GMTs will be 
presented. 
Further, a determination of the N9 NA content of the 2017 H7N9 IIV and the N1 and N2 content 
of seasonal licensed QIV is planned, and if successful, may be used to correlate the N1, N2 and 
N9 NA elicited antibody responses to the NA content of the 2017 H7N9 IIV and seasonal IIV4, 
respectively. Detectable NA antibody responses and GMTs will be summarized stratified by NA 
content, and statistical modeling may be used to examine the relationship of NA response with 
NA vaccine content, and study vaccination schedule.  
At least a subset of samples will also be tested for cross-reactive serum HAI and Neut antibody 
responses to antigenically drifted variants of influenza A/H7 viruses. Strain-specific results will 
be summarized using descriptive statistics as described above, correlations with 2017 H7N9 
responses, and association with study vaccine dose and adjuvant.  
Further immunogenicity testing and/or analyses may be carried out in the future based upon 
subjects’ prior receipt of non-seasonal influenza vaccines, including type (inactivated or live 
attenuated), what subtype (e.g. A/H3, A/H5, A/H9) and approximate date of vaccination. 
11.6.4 
Missing Values and Outliers 
All attempts will be made to collect all data per protocol. As missing data are expected to be 
minimal, no imputation will be performed for missing values. Any data point that appears to be 
erroneous or inexplicable based on clinical judgment will be investigated as a possible outlier. If 
data points are identified as outliers, sensitivity analyses will be performed to examine the 
impact of including or excluding the outliers. Any substantive differences in these analyses will 
be reported. 


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


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


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


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procedures and study interventions/products. This will include the nature, risks and possible 
benefits of this trial, alternate therapies, any known AEs, the investigational status of the study 
interventions/products, and the other elements that are part of obtaining proper informed consent. 
Subjects will also receive a detailed explanation of the proposed use and disclosure of their 
protected health information, including specifically their serum samples. Subjects will be 
allowed sufficient time to consider participation in this research trial, after having the nature, 
risks, and possible benefits of this trial explained to them, and have the opportunity to discuss 
this trial with their family, friends, or legally authorized representative, or think about it prior to 
agreeing to participate. 
ICFs describing in detail the study interventions/products, study procedures, risks, and possible 
benefits will be given to subjects. The ICF must not include any exculpatory statements. ICFs 
will be IRB-approved and subjects will be asked to read and review the appropriate document. 
Upon reviewing the appropriate document, the site principal investigator (or designee) will 
explain this research trial to subjects and answer any questions that may arise. Subjects must sign 
the ICF, and written documentation of the informed consent process is required prior to starting 
any study procedures being done specifically for this trial, including determining eligibility and 
administering study product. 
By signing the ICF, subjects agree to complete all study procedures required by this trial, unless 
the subject withdraws voluntarily, or is withdrawn or terminated from this trial for any reason. 
The rights and welfare of subjects will be protected by emphasizing to subjects that the quality of 
their medical care will not be adversely affected if they decline to participate in or withdraw 
from this trial. 
DMID will provide the site principal investigator, in writing, any new information that 
significantly impacts the subject’s risk of receiving the investigational products. This new 
information will be communicated by the site principal investigator to subjects who consent to 
participate in this trial in accordance with IRB requirements. The ICF will be updated and 
subjects will be re-consented per IRB requirements, if necessary. Subjects will be given a copy 
of all ICFs that they sign. 
14.4 
Exclusion of Women, Minorities, and Children (Special Populations) 
This trial will be inclusive of all subjects ages 19-64 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 [80]. Should the outcome of this trial be 
deemed acceptable, additional trials may be initiated including those in other populations. 


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It is unknown if the 2017 H7N9 IIV with or without AS03 adjuvant poses any risks to an unborn 
child. As of November 22, 2015 (per the most current version of the manufacturer’s IB), the 
available data for women who become pregnant during clinical trials of AS03-adjuvanted (pre) 
pandemic influenza vaccines do not suggest any causal relationship between adverse pregnancy 
outcomes and receipt of an AS03-adjuvanted vaccine. Women of childbearing potential who are 
not sterilized via tubal ligation, bilateral oophorectomy, salpingectomy,  hysterectomy, or 
successful Essure® placement (permanent, non-surgical, non-hormonal sterilization) with 
documented radiological confirmation test at least 90 days after the procedure, and still 
menstruating or who are not postmenopausal for ≥1 year must use an acceptable contraception 
method that may include, but is not limited to, non-male sexual relationships, abstinence from 
sexual intercourse with a male partner, monogamous relationship with a vasectomized partner 
who has been vasectomized for at least 180 days prior to the subject receiving the first study 
vaccination, barrier methods such as condoms or diaphragms with spermicide or foam, , effective 
intrauterine devices, NuvaRing® and licensed hormonal methods, such as implants, injectables, 
or oral contraceptives (“the pill”) for a minimum of 30 days prior to study product exposure and 
agree to practice highly effective contraception for the duration of study product exposure, 
including 60 days after their last study vaccination. A highly effective method of contraception is 
defined as one that results in a low failure rate (i.e., less than 1% per year) when used 
consistently and correctly. In addition to contraceptive use, all women of childbearing potential 
will be required to have a negative urine or serum pregnancy test within 24 hours prior to each 
study vaccination. If a female subject becomes pregnant while participating in this trial, we will 
ask her permission to follow-up with her about her health and the health of her baby through 
pregnancy outcome. 
Children will not be included in this trial as presently there are no safety or efficacy data in 
adults. 
14.5 
Subject Confidentiality 
Subject confidentiality is strictly held in trust by the site principal investigators, other study 
personnel, the sponsor, and their agents. This confidentiality is extended to cover testing of 
biological samples, in addition to the clinical information relating to participating subjects. 
Subjects will have code numbers and will not be identified by name. 
The study protocol, documentation, data, and all other information generated will be held in 
strict confidence. No information concerning this trial or the data will be released to any 
unauthorized third party without prior written approval of the sponsor. 
All information provided by the sponsor and all data and information generated by the 
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confidential by the site principal investigators and other study personnel to the extent permitted 
by law. These restrictions do not apply to: (1) information which becomes publicly available 
through no fault of the site principal investigators or other study personnel; (2) information 
which is necessary to disclose in confidence to an IRB solely for the evaluation of this trial; (3) 
information which is necessary to disclose in order to provide appropriate medical care to a study 
subject; or (4) study results which may be published as described in Section 17.  
The study monitor, applicable regulatory authorities, such as the FDA, or other authorized 
representatives of the sponsor may inspect all documents and records required to be maintained 
by the site principal investigators. This 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. 
To protect privacy, we have received a Certificate of Confidentiality.  With this Certificate, the 
researchers cannot be forced to release information that may identify the research subject, even 
by a court subpoena, in any federal, state, or local civil, criminal, administrative, legislative, or 
other proceedings.  The researchers will use the Certificate to resist any demands for information 
that would identify the subject, except as explained below. 
The Certificate cannot be used to resist a demand for information from personnel of the United 
States Government that is used for auditing or evaluation of federally funded projects, like this 
study, or for information that must be released in order to meet the requirements of the Federal 
Food and Drug Administration (FDA). 
A Certificate of Confidentiality does not prevent the subject from voluntarily releasing 
information about themselves or their involvement in this research.  If any person or agency 
obtains a written consent to receive research information, then the researchers may not use the 
Certificate to withhold that information.   
The Certificate of Confidentiality does not prevent the researchers from reporting without the 
subject’s consent, information that would identify the subject as a participant in the research 
project regarding matters that must be legally reported including: child and elder abuse, sexual 
abuse, or wanting to harm themselves or others.   
 
14.6 
Study Discontinuation 
If this trial is discontinued, subjects, who have signed the 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. 


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14.7 
Costs, Subject Compensation, and Research Related Injuries 
There is no cost to subjects for taking part in this trial. 
Subjects may be compensated for their participation in this trial. Compensation will be in 
accordance with the local IRB’s policies and procedures, and subject to IRB approval. 
If it is determined by the participating VTEU site and the site principal investigator that an injury 
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 the participating VTEU site for any injury suffered due to participation in this 
trial. 
For this protocol, the study products (monovalent inactivated influenza 2017 H7N9 virus vaccine 
manufactured by Sanofi Pasteur and adjuvant (AS03) manufactured by GSK), are covered under 
the Public Readiness and Emergency Preparedness Act (PREP Act), as described in Section 
2.1.1. 
 
14.8 
Future Use of Stored Specimens 
Residual samples/specimens are those that are left over after the study has been completed. 
Subjects may be asked for permission to keep any remaining (residual) clinical samples (serum) 
derived from venous blood samples for possible use in future research studies, such as examining 
additional immunological assessments or testing for antibodies against other viruses or bacteria, 
or the retention of those samples for possible future use may be a condition of study 
participation. Residual clinical samples for future use will be stored indefinitely at a central 
clinical storage facility and may be shared for purposes other than per protocol analysis with 
investigators at the participating VTEU site and with other investigators at other institutions once 
the clinical study report has been finalized. 
Other blood samples are being collected during the study specifically for future use, from 
subjects who consent to collection of those specimens either by signing an informed consent 
form that includes collection of future use samples as a condition of study participation or by 
indicating that they opt in to sample collection for future use if the informed consent form allows 
the option to choose that option. It is anticipated that up to ten 0.5 mL aliquots of serum from 


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each extra 10 mL venous blood sample will be available specifically for the purpose of future 
research, including but not limited to non-traditional immune assay development, assessing 
innate immune factors and the ability of H7 vaccine-induced antibodies to cross-react with other 
influenza viruses. These future research clinical samples will be stored indefinitely at a central 
clinical storage facility. 
Unlike residual samples, samples/specimens collected during the study solely for the purpose of 
future research may be requested from DMID and shipped from the DMID CMS at any time. 
The samples (residual and the extra venous blood sample collected solely for future use) will not 
be sold or used directly for production of any commercial product. No genetic tests will be 
performed on samples. Each sample will be encoded (labeled) only with a barcode and a unique 
tracking number to protect subject confidentiality. 
There are no benefits to subjects in the collection, storage and subsequent use of their specimens 
for future research. Reports about future research done with subjects’ samples will NOT be kept 
in their health records. 
Subjects who are provided the option to decide if residual samples may be retained for possible 
future use or if other blood specimens may be collected specifically for future use may change 
those decisions at any time by notifying the study doctors or nurses in writing. However, if the 
subject originally consents to future use of residual samples or collection of samples specifically 
for future research, and subsequently changes his/her decision, any data from a previously 
collected sample may still be used for this research. 


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15 
DATA HANDLING AND RECORD KEEPING 
The site principal investigator is responsible to ensure the accuracy, completeness, legibility, and 
timeliness of the data reported. 
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 principal investigators 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 principal investigator or 
appropriate sub-investigator. 
Data collection is the responsibility of the study personnel at each participating VTEU site under 
the supervision of the respective site principal investigator. During this trial, the site principal 
investigator must maintain complete and accurate documentation for this trial. 
The SDCC for this trial will be responsible for data management, quality review, analysis, and 
reporting of the study data. 
15.2 
Data Capture Methods 
Clinical (including, but not limited to, AE/SAEs, concomitant medications, medical history, 
physical assessments, and clinical laboratory values), reactogenicity and immunogenicity data 
will be entered into a 21 CFR 11-compliant Internet Data Entry System provided by the SDCC. 
The data system includes password protection and internal quality checks, such as automatic 


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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, reactogenicity and immunogenicity data). 
15.4 
Timing/Reports 
Clinical, safety and reactogenicity data through approximately 21 days after the second 
adjuvanted H7N9 study vaccination for Groups 1 and 2 will represent the primary clinical 
database for this trial. Once the last subject completes the visit that occurs approximately 21 days 
after the last adjuvanted H7N9 study vaccination, the primary clinical database will be cleaned, 
monitored and locked. Analyses of safety, reactogenicity, and primary and secondary 
immunogenicity data by treatment are planned. A preliminary report will be prepared by the 
SDCC after the primary clinical database is locked and all HAI and Neut data through 21 days 
after the last study vaccination are received. These analyses may be made available to the 
sponsor for planning subsequent trials and to the lead principal investigator for publication. 
These analyses will not be used to make any decisions concerning the conduct of this trial. All 
analyses of data included in the preliminary report for early release will be considered the final 
analysis of these data, and also included in the final CSR. 
Analysis of exploratory immunogenicity endpoints may be performed and released as the data is 
available from the central clinical laboratory. Any such analyses would be considered the final 
analysis for the endpoint, and included in the CSR. 
The final CSR will be completed after the last subject’s last visit is completed, and the final 
clinical database including all long-term safety follow-up data is cleaned, monitored and locked. 
Additional exploratory immunogenicity endpoint data not available at the time of CSR 
preparation may be included in an addendum to the CSR. 
Additional statistical reports may be generated as deemed necessary and appropriate by DMID. 
Safety and immunogenicity summary reports may be generated for the DSMB. 
After the final CSR is complete, and upon request and DMID approval, the SDCC will provide 
the participating VTEU sites with a summary of results by treatment arm and/or subject 
treatment assignments. In this regard, the participating VTEU sites requesting such information 
to share with study subjects must do so in compliance with their respective IRB guidelines. 


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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. ICFs for future use will be maintained as long as 
the sample exists. 
The participating VTEU sites must contact DMID for authorization prior to the destruction of 
any study records.  


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


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


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China. Emerg Infect Dis, 2014. 20(8): p. 1315-8. 
52. 
Gao, R., et al., Human infection with a novel avian-origin influenza A (H7N9) virus. N 
Engl J Med, 2013. 368(20): p. 1888-97. 
53. 
Analysis of recent scientific information on avian influenza A(H7N9) virus. WHO  
Influenza Update, 2017. 
54. 
Human infection with avian influenza A(H7N9) virus – China: 07 December 2017. WHO  
Emergencies preparedness, response, 2017. 
55. 
WHO Emergencies preparedness, response- Disease Outbreak News 5 April 2017. 
56. 
Zhou, J., et al., Biological features of novel avian influenza A (H7N9) virus. Nature, 
2013. 499(7459): p. 500-3. 
57. 
Zhu, H., et al., Infectivity, transmission, and pathology of human-isolated H7N9 influenza 
virus in ferrets and pigs. Science, 2013. 341(6142): p. 183-6. 
58. 
Li, Y., et al., Evolving HA and PB2 genes of influenza A (H7N9) viruses in the fifth wave 
- Increasing threat to both birds and humans? J Infect, 2017. 
59. 
Hoskins, T.W., et al., Controlled trial of inactivated influenza vaccine containing the a-
Hong Kong strain during an outbreak of influenza due to the a-England-42-72 strain. 
Lancet, 1973. 2(7821): p. 116-20. 
60. 
Hoskins, T.W., et al., Influenza at Christ's Hospital: March, 1974. Lancet, 1976. 1(7951): 
p. 105-8. 
61. 
Belongia, E.A., et al., Repeated annual influenza vaccination and vaccine effectiveness: 
review of evidence. Expert Rev Vaccines, 2017. 16(7): p. 1-14. 
62. 
Keitel, W.A., et al., Efficacy of repeated annual immunization with inactivated influenza 
virus vaccines over a five year period. Vaccine, 1997. 15(10): p. 1114-22. 
63. 
Ohmit, S.E., et al., Influenza vaccine effectiveness in the community and the household. 
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64. 
Langley, J.M., et al., A randomized, controlled non-inferiority trial comparing 
A(H1N1)pmd09 vaccine antigen, with and without AS03 adjuvant system, co-
administered or sequentially administered with an inactivated trivalent seasonal 
influenza vaccine. BMC Infect Dis, 2012. 12: p. 279. 
65. 
Peeters, M., et al., Safety and immunogenicity of an AS03-adjuvanted A(H1N1)pmd09 
vaccine administered simultaneously or sequentially with a seasonal trivalent vaccine in 
adults 61 years or older: data from two multicentre randomised trials. Vaccine, 2012. 
30(45): p. 6483-91. 
66. 
Roy-Ghanta, S., et al., Responses to A(H1N1)pdm09 influenza vaccines in participants 
previously vaccinated with seasonal influenza vaccine: a randomized, observer-blind, 
controlled study. J Infect Dis, 2014. 210(9): p. 1419-30. 
67. 
Uno, S., et al., Effect of prior vaccination with a seasonal trivalent influenza vaccine on 
the antibody response to the influenza pandemic H1N1 2009 vaccine: a randomized 
controlled trial. Microbiol Immunol, 2011. 55(11): p. 783-9. 


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Version 5.0 
Co-Administration of AS03-adjuvanted A/H7N9 with IIV4 
September 18, 2018 
 
142 
68. 
Chen, W.H., et al., Phase 2 assessment of the safety and immunogenicity of two 
inactivated pandemic monovalent H1N1 vaccines in adults as a component of the U.S. 
pandemic preparedness plan in 2009. Vaccine, 2012. 30(28): p. 4240-8. 
69. 
Vajo, Z., et al., Safety and immunogenicity of a 2009 pandemic influenza A H1N1 vaccine 
when administered alone or simultaneously with the seasonal influenza vaccine for the 
2009-10 influenza season: a multicentre, randomised controlled trial. Lancet, 2010. 
375(9708): p. 49-55. 
70. 
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. 
71. 
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. 
72. 
Haber, P., et al., Guillain-Barre syndrome following influenza vaccination. JAMA, 2004. 
292(20): p. 2478-81. 
73. 
De Wals, P., et al., Risk of Guillain-Barre syndrome following H1N1 influenza 
vaccination in Quebec. JAMA, 2012. 308(2): p. 175-81. 
74. 
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. 
75. 
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. 
76. 
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. 
77. 
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. 
78. 
Dodd, C.N., et al., International collaboration to assess the risk of Guillain Barre 
Syndrome following Influenza A (H1N1) 2009 monovalent vaccines. Vaccine, 2013. 
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79. 
Sullivan, S.S., Narcolepsy in adolescents. Adolesc Med State Art Rev, 2010. 21(3): p. 
542-55, x-xi. 
80. 
CDC, Recommended Immunizations for Adults: By Age. 2017. 
 


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143 
APPENDICES 
Appendix A: Schedule of Study Procedures and Evaluations 
Appendix B: List of Potentially Immune-Mediated Medical Conditions 
 


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APPENDIX A: SCHEDULE OF STUDY PROCEDURES AND 
EVALUATIONS 
Study Schedule, Group 1:  Vaccination Period  
Study Visit 
Number 
V00 
V01 
V02 
V03 
V04ψ 
V05 
V06 
Study Day post 
Dose 1 
Screening 
(Optional) 
D -28 to -1 
Enrollment 
Dose 1 
D1 
D4[±1] 
D8[+2] 
D22[+7] 
D25 
D29 
Study Day post 
Dose 2 
 
 
 
 
Dose 2 
D1 
D4[±1] 
D8[+2] 
Obtain Informed 
Consent∞ 
X 
X¬ 
 
 
 
 
 
Collect 
Demographic 
Information 
X 
X†* 
 
 
 
 
 
Review 
Eligibility 
Criteria 
X 
X†¬1 
 
 
X† 
 
 
Medical History@ 
X 
X†¬* 
 
X 
X 
 
X 
Concomitant 
Medications 
Xς 
X†¬ς 
Xς 
Xς 
Xς 
Xς 
Xς 
Vital Signs$ 
(Oral 
Temperature%, 
Pulse, and BP) 
X 
X† 
 
 
X†2 
 
 
Height and 
Weight 
X 
X†* 
 
 
 
 
 
Physical 
Examination3 
X 
{X}†* 
 
{X} 
{X} 
 
{X} 
Urine or Serum 
Pregnancy Test 
X^ 
X†^ 
 
 
X†^ 
 
 
Venous Blood 
Collection for 
ESR 
X 
X≠* 
 
 
 
 
 
Venous Blood 
Collection for 
Clinical Safety 
Laboratory 
Evaluations~ 
 
X† 
 
X 
X† 
 
X 
Venous Blood 
Collection for 
Immunogenicity 
Assays 
 
X† 
 
 
X† 
 
 
Serum Sample 
Collected for 
Future Research4 
 
X† 
 
X 
X† 
 
X 
Safety Follow-up 
Phone Call 
 
 
X 
 
 
X 
 


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145 
Study Visit 
Number 
V00 
V01 
V02 
V03 
V04ψ 
V05 
V06 
Study Day post 
Dose 1 
Screening 
(Optional) 
D -28 to -1 
Enrollment 
Dose 1 
D1 
D4[±1] 
D8[+2] 
D22[+7] 
D25 
D29 
Study Day post 
Dose 2 
 
 
 
 
Dose 2 
D1 
D4[±1] 
D8[+2] 
Enrollment in 
AdvantageEDCSM 
and 
Randomization 
 
X† 
 
 
 
 
 
Pre-
Administration 
Reactogenicity 
Assessments 
 
X† 
 
 
X 
 
 
 Vaccination 
 
X 
 
 
X 
 
 
20-minute 
Evaluation After 
Study 
Vaccination 
 
X 
 
 
X 
 
 
Examine Study 
Vaccination Site 
 
X 
 
X 
X 
 
X 
Post-
Administration 
Reactogenicity 
Assessments 
 
X 
 
 
X 
 
 
Distribute 
Memory Aid and 
Study-Related 
Materials 
 
X 
 
 
X 
 
 
Review Memory 
Aid 
 
 
X 
X 
 
X 
X 
AE/SAE 
Assessment  
 
X& 
X& 
X& 
X& 
X& 
X& 
∞ Prior to study procedures. 
† Prior to study vaccination.  
1 Review results of clinical screening (ESR) or safety laboratory evaluations. 
¬ Review/confirm information or activity in subjects previously consented and screened. 
@ Complete medical history will be obtained by interview of subjects at screening (optional) or on Day 1 prior to the first study 
vaccination and interim medical history will be obtained by interview of subjects at follow-up visits after Dose 1 
ς  Receipt of non-study influenza vaccines will be solicited through approximately 180 days after the last study vaccination, and 
reported in the eCRF. 
* Not required if done at the optional screening visit. 
√ All current medications and medications taken within 60 days prior to signing the ICF. 
$ Vital signs assessed on Day 1 prior to the first study vaccination will be considered as baseline. 
% Subjects must not eat or drink anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
2 Vital signs are not required for subjects who are discontinued from receipt of the third study vaccination and are being 
followed for safety. 
3 At the screening (or baseline if not done at screening) visit, a physical examination will be performed on all subjects to 
include the following organs and organ systems: skin, head and neck, lungs, heart, liver, spleen, extremities, lymph nodes, 
and nervous system. 
{} Targeted physical examination if indicated based on review of interim medical history. 
^ May be performed on all women of childbearing potential at screening (optional) and will be performed within 24 hours prior 
to each vaccination and results must be negative and known prior to each study vaccination. 


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146 
≠ To be performed locally by the site. The ESR value must be confirmed as <30 mm/hr prior to randomization and first study 
vaccination. 
~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr. 
Ψ  Subjects who do not receive the third study vaccination will continue with follow-up safety assessments (may be conducted by 
phone call) rather than in person continuing through approximately 12 months after their first study vaccination. These 
subjects will also be encouraged to provide a venous blood sample for immunogenicity assays at approximately 21 and 180 
days after their first study vaccination. 
4 For subjects who have consented to collected of serum for future research. 
& Inclusive of reactogenicity assessments performed on the day of each vaccination through 7 days after each study vaccination.  
 
Study Schedule, Group 1:  Follow-up Period  
Study Visit 
Number 
     
V07 
 
V08 
V09ψ 
V10 
V11 
Early 
Termination 
(if needed) 
Unscheduled 
(if needed) 
Study Day post 
Dose 1 
D43 
D64 
D181 
[±14] 
 D202 
 D387 
 
 
Study Day post 
Dose 2 
D22[+7] 
D43[+7] 
 
 D181[±14] 
     
D366[±14] 
 
 
Medical 
History@ 
X 
X 
X 
X 
 
X 
X (if indicated) 
Concomitant 
Medications 
Xς 
Xς 
Xς 
Xς 
 
X (if within 21 days 
after last study 
vaccination and 
receipt of any non-
study influenza 
vaccine will be 
recorded if within 
180 days after the 
2nd study 
vaccination) 
X (if within 21 
days after last 
study vaccination 
and receipt of any 
non-study 
influenza vaccine 
will be recorded 
if within 180 days 
after the 2nd 
study 
vaccination) 
Vital Signs$ 
(Oral 
Temperature%, 
Pulse, and BP) 
 
 
 
 
 
X (may be obtained 
if indicated) 
X (may be 
obtained if 
indicated) 
Physical 
Examination3 
{X} 
{X} 
{X} 
{X} 
 
{X} 
{X} 
Venous Blood 
Collection for 
Clinical Safety 
Laboratory 
Evaluations~ 
 
 
 
 
 
X (if within 7 days 
after the last study 
vaccination) 
X (if indicated) 
Venous Blood 
Collection for  
Immunogenicity  
Assays 
X 
 
X 
X 
 
X(if within 21 days 
after last study 
vaccination 
X(if within 21 
days after last 
study vaccination 
Serum Sample 
Collected for 
Future Research4 
X 
X 
X 
X 
 
X(if within 21 days 
after last  study 
vaccination 
X(if within 21 
days after last  
study vaccination   


DMID Protocol 17-0077 
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September 18, 2018 
 
147 
@ Complete medical history will be obtained by interview of subjects at screening (optional) or on Day 1 prior to the first study 
vaccination and interim medical history will be obtained by interview of subjects at follow-up visits after Dose 1 
ς  Receipt of non-study influenza vaccines will be solicited through approximately 180 days after the last study vaccination, and 
reported in the eCRF. 
$ Vital signs assessed on Day 1 prior to the first study vaccination will be considered as baseline. 
% Subjects must not eat or drink anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
{} Targeted physical examination if indicated based on review of interim medical history 
.~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr. 
Ψ  Subjects who do not receive the third study vaccination will continue with follow-up safety assessments (may be conducted by 
phone call) rather than in person continuing through approximately 12 months after their first study vaccination. These 
subjects will also be encouraged to provide a venous blood sample for immunogenicity assays at approximately 21 and 180 
days after their first study vaccination. 
4 For subjects who have consented to collected of serum for future use. 
 
Study Schedule, Group 2:  Vaccination Period 
Study Visit Number 
V00 
V01 
V02 
V03 
V04ψ 
V05 
V06 
V07ψ 
V08 
Study Day post Dose 1 
Screening 
(Optional) 
D -28 to -1 
Enrollment  
Dose 1 
D1 
D4[±1] 
D8[+2] 
D22[+7] 
D25  
D29 
D43 
D46 
Study Day post Dose 2 
 
 
 
 
Dose 2 
D1 
D4[±1] 
D8[+2] 
D22[+7] 
D25 
Study Day post Dose 3 
 
 
 
 
 
 
 
Dose 3 
D1 
D4[±1] 
Study Procedure/Evaluation 
 
Obtain Informed 
Consent∞ 
X 
X¬ 
 
 
 
 
 
 
 
Collect Demographic 
Information 
X 
X†* 
 
 
 
 
 
 
 
Review Eligibility 
Criteria 
X 
X†¬1 
 
 
X† 
 
 
X† 
 
Medical History@ 
X 
X†¬* 
 
X 
X 
 
X 
X 
 
Safety Follow-
up Phone Call 
 
 
 
 
 
X 
 
 
Examine Study 
Vaccination Site 
 
 
 
 
 
X (if within 7 days 
after last study 
vaccination) 
X (if within 7 
days after last 
study 
vaccination) 
Post-
Administration 
Reactogenicity 
Assessments 
 
 
 
 
 
X (if within 7 days 
after last study 
vaccination) 
X (if within 7 
days after last 
study 
vaccination) 
Review Memory 
Aid 
 
 
 
 
 
X (if within 7 days 
after last study 
vaccination) 
X (if within 7 
days after last 
study 
vaccination) 
AE/SAE 
Assessment 
X 
X 
X 
X 
X 
X& 
X& 


DMID Protocol 17-0077 
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148 
Study Visit Number 
V00 
V01 
V02 
V03 
V04ψ 
V05 
V06 
V07ψ 
V08 
Study Day post Dose 1 
Screening 
(Optional) 
D -28 to -1 
Enrollment  
Dose 1 
D1 
D4[±1] 
D8[+2] 
D22[+7] 
D25  
D29 
D43 
D46 
Study Day post Dose 2 
 
 
 
 
Dose 2 
D1 
D4[±1] 
D8[+2] 
D22[+7] 
D25 
Study Day post Dose 3 
 
 
 
 
 
 
 
Dose 3 
D1 
D4[±1] 
Study Procedure/Evaluation 
 
Concomitant Medications 
Xς 
X†¬ς 
Xς 
Xς 
Xς 
Xς 
Xς 
Xς 
Xς 
Vital Signs$ 
(Oral Temperature%, 
Pulse, and BP) 
X 
X† 
 
 
X†2 
 
 
X†2 
 
Height and Weight 
X 
X†* 
 
 
 
 
 
 
 
Physical Examination3 
X 
X†* 
 
{X} 
{X} 
 
{X} 
{X} 
 
Urine or Serum 
Pregnancy Test 
X^ 
X†^ 
 
 
X†^ 
 
 
X†^ 
 
Venous Blood Collection 
for ESR 
X 
X≠* 
 
 
 
 
 
 
 
Venous Blood Collection 
for Clinical Safety 
Laboratory Evaluations~ 
 
X† 
 
X 
X† 
 
X 
X† 
 
Venous Blood Collection 
for Immunogenicity 
Assays 
 
X† 
 
 
X† 
 
 
X† 
 
Serum Sample Collected 
for Future Research4 
 
X† 
 
X 
X† 
 
X 
X† 
 
Safety Follow-up Phone 
Call 
 
 
X 
 
 
X 
 
 
X 
Enrollment in 
AdvantageEDCSM and 
Randomization 
 
X† 
 
 
 
 
 
 
 
Pre-Administration 
Reactogenicity 
Assessments 
 
X† 
 
 
X 
 
 
X 
 
Vaccination 
 
X 
 
 
X 
 
 
X 
 
20-minute Evaluation 
After Vaccination 
 
X 
 
 
X 
 
 
X 
 
Examine Vaccination Site 
 
X 
 
X 
X 
 
X 
X 
 


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149 
Study Visit Number 
V00 
V01 
V02 
V03 
V04ψ 
V05 
V06 
V07ψ 
V08 
Study Day post Dose 1 
Screening 
(Optional) 
D -28 to -1 
Enrollment  
Dose 1 
D1 
D4[±1] 
D8[+2] 
D22[+7] 
D25  
D29 
D43 
D46 
Study Day post Dose 2 
 
 
 
 
Dose 2 
D1 
D4[±1] 
D8[+2] 
D22[+7] 
D25 
Study Day post Dose 3 
 
 
 
 
 
 
 
Dose 3 
D1 
D4[±1] 
Study Procedure/Evaluation 
 
Post-Administration 
Reactogenicity 
Assessments 
 
X 
 
 
X 
 
 
X 
 
Distribute Memory Aid 
and Study-Related 
Materials 
 
X 
 
 
X 
 
 
X 
 
Review Memory Aid 
 
 
X 
X 
 
X 
X 
 
X 
AE/SAE Assessment  
 
X& 
X& 
X& 
X& 
X& 
X& 
X& 
X& 
∞ Prior to study procedures. 
† Prior to study vaccination.  
1 Review results of clinical screening (ESR) or safety laboratory evaluations. 
¬ Review/confirm information or activity in subjects previously consented and screened. 
@ Complete medical history will be obtained by interview of subjects at screening (optional) or on Day 1 prior to the first study 
vaccination and interim medical history will be obtained by interview of subjects at follow-up visits after the first study 
vaccination. 
ς  Receipt of non-study influenza vaccines will be solicited through approximately 180 days after the last study vaccination, and 
reported in the eCRF. 
* Not required if done at the optional screening visit. 
√ All current medications and medications taken within 60 days prior to signing the ICF. 
$ Vital signs assessed on Day 1 prior to the first study vaccination will be considered as baseline. 
% Subjects must not eat or drink anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
2 Vital signs are not required for subjects who are discontinued from receipt of the third study vaccination and are being 
followed for safety. 
3 At the screening (or baseline if not done at screening) visit, a physical examination will be performed on all subjects to 
include the following organs and organ systems: skin, head and neck, lungs, heart, liver, spleen, extremities, lymph nodes, 
and nervous system. 
{} Targeted physical examination if indicated based on review of interim medical history. 
^ May be performed on all women of childbearing potential at screening (optional) and will be performed within 24 hours prior 
to each vaccination and results must be negative and known prior to each study vaccination. 
≠ To be performed locally by the site. The ESR value must be confirmed as <30 mm/hr prior to randomization and first study 
vaccination. 
~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr. 
Ψ  Subjects who do not receive the third study vaccination will continue with follow-up safety assessments (may be conducted by 
phone call) rather than in person continuing through approximately 12 months after their first study vaccination. These 
subjects will also be encouraged to provide a venous blood sample for immunogenicity assays at approximately 21 and 180 
days after their first study vaccination. 
4 For subjects who have consented to collected of serum for future use. 
& Inclusive of reactogenicity assessments performed on the day of each vaccination through 7 days after each study vaccination.  
 
Study Schedule, Group 2:  Follow-up Period 


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September 18, 2018 
 
150 
@ Complete medical history will be obtained by interview of subjects at screening (optional) or on Day 1 prior to the first study 
vaccination and interim medical history will be obtained by interview of subjects at follow-up visits after the first study 
vaccination. 
ς  Receipt of non-study influenza vaccines will be solicited through approximately 180 days after the last study vaccination, and 
reported in the eCRF. 
$ Vital signs assessed on Day 1 prior to the first study vaccination will be considered as baseline. 
% Subjects must not eat or drink anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
{} Targeted physical examination if indicated based on review of interim medical history. 
~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr. 
Study Visit Number 
V09 
V10 
V11ψ 
V12 
V13 
Early 
Terminati
on (if 
needed) 
Unschedu
led (if 
needed) 
Study Day post Dose 
1 
D50 
D64 
D181 [±14] 
D223 
D408 
 
 
Study Day post Dose 
2 
D29 
D43 
 
D202 
D387 
 
 
Study Day post Dose 
3 
 D8[+2] 
 D22[+7] 
 
D181[±14] 
D366[±14] 
 
 
Medical History@ 
X 
X 
X 
X 
 
X 
X (if indicated) 
Concomitant 
Medications 
Xς 
Xς 
Xς 
Xς 
 
X (if within 21 days after last 
study vaccination and receipt 
of any non-study influenza 
vaccine will be recorded if 
within 180 days after the 2nd 
study vaccination) 
X (if within 21 days after last 
study vaccination and receipt 
of any non-study influenza 
vaccine will be recorded if 
within 180 days after the 2nd 
study vaccination) 
Vital Signs$ 
(Oral Temperature%, 
Pulse, and BP) 
 
 
 
 
 
X (may be obtained if 
indicated) 
X (may be obtained if 
indicated) 
Physical Examination3 
{X} 
{X} 
{X} 
{X} 
 
{X} 
{X} 
Venous Blood 
Collection for Clinical 
Safety Laboratory 
Evaluations~ 
X 
 
 
 
 
X (if within 7 days after the 
last study vaccination) 
X (if indicated) 
Venous Blood 
Collection for  
Immunogenicity  
Assays 
 
X 
X 
X 
 
X(if within 21 days after last 
study vaccination 
X(if within 21 days after last 
study vaccination 
Serum Sample 
Collected for Future 
Research4 
X 
X 
X 
X 
 
X(if within 21 days after last  
study vaccination 
X(if within 21 days after last  
study vaccination 
Safety Follow-up 
Phone Call 
 
 
 
 
X 
 
 
Examine Vaccination 
Site 
X 
 
 
 
 
X (if within 7 days after last 
study vaccination) 
X (if within 7 days after last 
study vaccination) 
Post-Administration 
Reactogenicity 
Assessments 
 
 
 
 
 
X (if within 7 days after last 
study vaccination) 
X (if within 7 days after last 
study vaccination) 
Review Memory Aid 
X 
 
 
 
 
X (if within 7 days after last 
study vaccination) 
X (if within 7 days after last 
study vaccination) 
AE/SAE Assessment 
X& 
X 
X 
X 
X 
X& 
X& 


DMID Protocol 17-0077 
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September 18, 2018 
 
151 
Ψ  Subjects who do not receive the second or third study vaccination will continue with follow-up safety assessments (may be 
conducted by phone call) rather than in person continuing through approximately 12 months after their first study vaccination. 
These subjects will also be encouraged to provide a venous blood sample for immunogenicity assays at approximately 21 and 
180 days after their first study vaccination. 
4 For subjects who have consented to collected of serum for future use 
& Inclusive of reactogenicity assessments performed on the day of each study vaccination through 7 days after each study 
vaccination.  
 
Study Schedule, Group 3:  Vaccination and Follow-up Periods 
Study Visit Number 
V00 
V01 
V02 
V03 
 
V04ψ 
 
V05 
 
V06 
 
V07ψ 
 
V08 
Study Day post  
 dose 
Screening 
(Optional) 
D -28 to -1 
Enrollment 
Dose 1 
D1 
D4[±1] 
D8[+2] 
 
D22[+7] 
 
D43[+7] 
 
D64[+7] 
 
D181[±14] 
 
D366[±14] 
Obtain Informed Consent 
X 
X¬ 
 
 
 
 
 
 
 
Collect Demographic 
Information 
X 
X†* 
 
 
 
 
 
 
 
Review Eligibility Criteria 
X 
X†¬1 
 
 
 
 
 
 
 
Medical History@ 
X 
X†¬* 
 
X 
X 
X 
X 
X 
 
Concomitant Medications 
Xς 
X†¬ς 
Xς 
Xς 
Xς 
 
Xς 
Xς 
 
Xς 
 
 
 
Vital Signs$ 
(Oral Temperature%, Pulse, 
and BP) 
X 
X† 
 
 
 
 
 
 
 
Height and Weight 
X 
X†* 
 
 
 
 
 
 
 
Physical Examination3 
X 
{X}†* 
 
{X} 
{X} 
{X} 
{X} 
{X} 
 
Urine or Serum Pregnancy 
Test 
X^ 
X†^ 
 
 
 
 
 
 
 
Venous Blood Collection for 
ESR 
X 
X≠* 
 
 
 
 
 
 
 
Venous Blood Collection for 
Clinical Safety Laboratory 
Evaluations~ 
 
X 
 
X 
 
 
 
 
 
 
 
Venous Blood Collection for 
Immunogenicity Assays 
 
X† 
 
 
 
X 
 
 
 
 
 
X 
 
Serum Sample Collected for 
Future Research4 
 
X† 
 
X 
X 
X 
X 
X 
 
Safety Follow-up Phone Call 
 
 
X 
 
 
 
 
 
X 
Enrollment in 
AdvantageEDCSM and 
Randomization 
 
X† 
 
 
 
 
 
 
 
Pre-Administration 
Reactogenicity Assessments 
 
X† 
 
 
 
 
 
 
 
 Vaccination 
 
X 
 
 
 
 
 
 
 


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152 
Study Visit Number 
V00 
V01 
V02 
V03 
 
V04ψ 
 
V05 
 
V06 
 
V07ψ 
 
V08 
Study Day post  
 dose 
Screening 
(Optional) 
D -28 to -1 
Enrollment 
Dose 1 
D1 
D4[±1] 
D8[+2] 
 
D22[+7] 
 
D43[+7] 
 
D64[+7] 
 
D181[±14] 
 
D366[±14] 
20-minute Evaluation After 
Vaccination 
 
X 
 
 
 
 
 
 
 
Examine Vaccination Site 
 
X 
 
X 
 
 
 
 
 
Post-Administration 
Reactogenicity Assessments 
 
X 
 
 
 
 
 
 
 
Distribute Memory Aid and 
Study-Related Materials 
 
X 
 
 
 
 
 
 
 
Review Memory Aid 
 
 
X 
X 
 
 
 
 
 
AE/SAE Assessment  
 
X& 
X& 
X& 
X 
X 
X 
X 
X 
∞ Prior to study procedures. 
† Prior to study vaccination.  
1 Review results of clinical screening (ESR) or safety laboratory evaluations. 
¬ Review/confirm information or activity in subjects previously consented and screened 
@ Complete medical history will be obtained by interview of subjects at screening (optional) or on Day 1 prior to study 
vaccination and interim medical history will be obtained by interview of subjects at follow-up visits after the study 
vaccination. 
ς  Receipt of non-study influenza vaccines will be solicited through approximately 180 days after the study vaccination, and 
reported in the eCRF. 
* Not required if done at the optional screening visit. 
√ All current medications and medications taken within 60 days prior to signing the ICF. 
$ Vital signs assessed on Day 1 prior to the 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. 
3 At the screening (or baseline if not done at screening) visit, a physical examination will be performed on all subjects to 
include the following organs and organ systems: skin, head and neck, lungs, heart, liver, spleen, extremities, lymph nodes, 
and nervous system. 
{} Targeted physical examination if indicated based on review of interim medical history. 
^ May be performed on all women of childbearing potential at screening (optional) and will be performed within 24 hours prior 
to study vaccination and results must be negative. 
≠ To be performed locally by the site. The ESR value must be confirmed as <30 mm/hr prior to randomization and study 
vaccination. 
~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr. 
4 For subjects who have consented to collected of serum for future use. 
& Inclusive of reactogenicity assessments performed on the day of vaccination through 7 days after study vaccination.  
 
Early Termination and Unscheduled Visits, Group 3 
Study Visit Number 
 
Early Termination (if 
needed) 
Unscheduled (if 
needed) 
Study Day post dose 
Medical History@ 
X 
X (if indicated) 


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153 
 
 
 
 
 
 
 
 
@ Complete medical history 
will be obtained by interview 
of subjects at screening 
(optional) or on Day 1 prior to 
study vaccination and interim 
medical history will be 
obtained by interview of 
subjects at follow-up visits 
after the study vaccination. 
$ 
Vital signs assessed on Day 
1 prior to the 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. 
{} Targeted physical 
examination if indicated based 
on review of interim medical 
history. 
~ Includes WBC, Hgb, PLT, 
ALT, T. Bili, Cr. 
4 
For subjects who have 
consented to collected of serum 
for future use. 
& Inclusive of reactogenicity 
assessments performed on the 
day of vaccination through 7 
days after study vaccination.  
 
 
 
 
Concomitant 
Medications 
X (if within 21 days 
after last study 
vaccination and receipt 
of any non-study 
influenza vaccine will 
be recorded if within 
180 days after the 2nd 
study vaccination) 
X (if within 21 days after 
last study vaccination and 
receipt of any non-study 
influenza vaccine will be 
recorded if within 180 days 
after the 2nd study) 
Vital Signs 
(Oral Temperature%, 
Pulse, and BP) 
X (may be obtained if 
indicated) 
X (may be obtained if 
indicated) 
Physical 
Examination3 
{X} 
{X} 
Venous Blood 
Collection for 
Clinical Safety 
Laboratory 
Evaluations~ 
X (if within 7 days after 
the last study 
vaccination) 
X (if indicated) 
Venous Blood 
Collection for  
Immunogenicity  
Assays 
X (if within 21 days 
after last study 
vaccination) 
X (if within 21 days after 
last study vaccination) 
Serum Sample 
Collected for Future 
Research4 
X(if within 21 days 
after last study 
vaccination 
X(if within 21 days after 
last study vaccination 
Examine Vaccination 
Site 
X (if within 7 days after 
last study vaccination) 
X (if within 7 days after last 
study vaccination) 
Post-Administration 
Reactogenicity 
Assessments 
X (if within 7 days after 
last study vaccination) 
X (if within 7 days after last 
study vaccination) 
Review Memory Aid 
X (if within 7 days after 
last study vaccination) 
X (if within 7 days after last 
study vaccination) 
AE/SAE Assessment  
X& 
X& 


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154 
APPENDIX B: LIST OF POTENTIALLY IMMUNE-MEDIATED 
MEDICAL CONDITIONS 
(also known as Adverse Events of Special Interest (AESIs)) 
 
Gastrointestinal disorders 
• 
Celiac disease 
• 
Crohn’s disease 
• 
Ulcerative colitis 
• 
Ulcerative proctitis 
Liver disorders 
• 
Autoimmune cholangitis 
• 
Autoimmune hepatitis 
• 
Primary biliary cirrhosis 
• 
Primary sclerosing cholangitis 
Metabolic diseases 
• 
Addison’s disease 
• 
Autoimmune thyroiditis (including Hashimoto thyroiditis) 
• 
Diabetes mellitus type I 
• 
Grave's or Basedow’s disease 
Musculoskeletal disorders 
• 
Antisynthetase syndrome 
• 
Dermatomyositis 
• 
Juvenile chronic arthritis (including Still’s disease) 
• 
Mixed connective tissue disorder 
• 
Polymyalgia rheumatic 
• 
Polymyositis 
• 
Psoriatic arthropathy 
• 
Relapsing polychondritis 
• 
Rheumatoid arthritis 
• 
Scleroderma, including diffuse systemic form and CREST syndrome 
• 
Spondyloarthritis, including ankylosing spondylitis, reactive arthritis (Reiter's Syndrome) 
and undifferentiated spondyloarthritis 
• 
Systemic lupus erythematosus 


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


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156 
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  
17-0077: A Phase II Study in Healthy Adults (19-64 Years of Age) to Assess 
the Safety, Reactogenicity and Immunogenicity of Sequential or 
Simultaneous Intramuscular Administration of an AS03-adjuvanted 
A/H7N9 Inactivated Influenza Vaccine with Seasonal Influenza Vaccine 
 
 
 
 
17-0077: NCT03318315 
 
Version 1.0 
 
DATE: 14 November 2018 
 
THIS COMMUNICATION IS PRIVILEGED AND CONFIDENTIAL  
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
 
14 November 2018 
- ii - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
STUDY TITLE 
Protocol Number Code: 
DMID Protocol: 17-0077 
Development Phase: 
Phase II 
Products: 
Sanofi A/H7N9 Inactivated Influenza Vaccine  
GSK AS03 Adjuvant 
Seasonal influenza vaccine (IIV4) 
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: 
20 February 2018 
 
Clinical Trial Completion Date: 
Expected June 2019 
 
Date of the Analysis Plan: 
14 November 2018 
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: 17-0077  
Version 1.0 
 
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TABLE OF CONTENTS 
STUDY TITLE ........................................................................................................................................... II 
TABLE OF CONTENTS .......................................................................................................................... III 
LIST OF ABBREVIATIONS .................................................................................................................... VI 
1. 
PREFACE ............................................................................................................................................ 1 
2. 
INTRODUCTION ............................................................................................................................... 2 
2.1. 
Purpose of the Analyses ................................................................................................................ 2 
3. 
STUDY OBJECTIVES AND ENDPOINTS ....................................................................................... 3 
3.1. 
Study Objectives ........................................................................................................................... 3 
3.1.1. 
Primary ................................................................................................................................ 3 
3.1.2. 
Secondary ............................................................................................................................ 3 
3.1.3. 
Exploratory .......................................................................................................................... 3 
3.2. 
Endpoints ...................................................................................................................................... 4 
3.2.1. 
Primary ................................................................................................................................ 4 
3.2.2. 
Secondary ............................................................................................................................ 5 
3.2.3. 
Exploratory .......................................................................................................................... 5 
3.3. 
Study Definitions and Derived Variables ..................................................................................... 6 
4. 
INVESTIGATIONAL PLAN .............................................................................................................. 7 
4.1. 
Overall Study Design and Plan ..................................................................................................... 7 
4.2. 
Discussion of Study Design, Including the Choice of Control Groups ........................................ 8 
4.3. 
Selection of Study Population ....................................................................................................... 8 
4.4. 
Treatments ..................................................................................................................................... 8 
4.4.1. 
Treatments Administered .................................................................................................... 8 
4.4.2. 
Identity of Investigational Product ...................................................................................... 8 
4.4.3. 
Method of Assigning Subjects to Treatment Groups (Randomization) .............................. 8 
4.4.4. 
Selection of Doses in the Study ........................................................................................... 8 
4.4.5. 
Selection and Timing of Dose for Each Subject ................................................................. 9 
4.4.6. 
Blinding ............................................................................................................................... 9 
4.4.7. 
Prior and Concomitant Therapy .......................................................................................... 9 
4.4.8. 
Treatment Compliance ........................................................................................................ 9 
4.5. 
Immunogenicity and Safety Variables ........................................................................................ 10 
4.5.1. 
Safety Variables ................................................................................................................ 10 
4.5.2. 
Immunogenicity Variables ................................................................................................ 10 


Statistical Analysis Plan - DMID Protocol: 17-0077  
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TABLE OF CONTENTS (continued) 
 
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5. 
SAMPLE SIZE CONSIDERATIONS .............................................................................................. 12 
6. 
GENERAL STATISTICAL CONSIDERATIONS ........................................................................... 13 
6.1. 
General Principles ....................................................................................................................... 13 
6.2. 
Timing of Analyses ..................................................................................................................... 13 
6.2.1. 
Preliminary Report and CSR ............................................................................................. 13 
6.3. 
Analysis Populations ................................................................................................................... 14 
6.3.1. 
Safety Population .............................................................................................................. 14 
6.3.2. 
Modified Intention-to-Treat (mITT) Population ............................................................... 14 
6.3.3. 
Per Protocol Population ..................................................................................................... 14 
6.4. 
Covariates and Subgroups ........................................................................................................... 15 
6.5. 
Missing Data ............................................................................................................................... 15 
6.6. 
Interim Analyses and Data Monitoring ....................................................................................... 15 
6.6.1. 
Interim Safety Review ....................................................................................................... 15 
6.6.2. 
Interim Immunogenicity Review....................................................................................... 16 
6.7. 
Multicenter Studies ..................................................................................................................... 16 
6.8. 
Multiple Comparisons/Multiplicity ............................................................................................. 16 
7. 
STUDY SUBJECTS .......................................................................................................................... 17 
7.1. 
Subject Disposition ..................................................................................................................... 17 
7.2. 
Protocol Deviations ..................................................................................................................... 17 
8. 
IMMUNOGENICITY EVALUATION ............................................................................................ 18 
8.1. 
Primary Immunogenicity Analysis ............................................................................................. 18 
8.2. 
Secondary Immunogenicity Analyses ......................................................................................... 19 
8.3. 
Exploratory Immunogenicity Analyses....................................................................................... 19 
8.3.1. 
Covariate Analysis ............................................................................................................ 19 
8.3.2. 
Regression Modeling......................................................................................................... 19 
8.3.3. 
NA Serum Antibody Responses ........................................................................................ 20 
9. 
SAFETY EVALUATION ................................................................................................................. 21 
9.1. 
Demographic and Other Baseline Characteristics ....................................................................... 21 
9.1.1. 
Prior and Concurrent Illnesses and Medical Conditions ................................................... 21 
9.1.2. 
Prior and Concurrent Medications .................................................................................... 21 
9.2. 
Measurements of Treatment Compliance ................................................................................... 22 
9.3. 
Adverse Events ........................................................................................................................... 22 


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TABLE OF CONTENTS (continued) 
 
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9.3.1. 
Solicited Events and Symptoms ........................................................................................ 22 
9.3.2. 
Unsolicited Adverse Events .............................................................................................. 23 
9.4. 
Deaths, Serious Adverse Events and other Significant Adverse Events ..................................... 24 
9.5. 
Pregnancies ................................................................................................................................. 24 
9.6. 
Clinical Laboratory Evaluations ................................................................................................. 25 
9.7. 
Vital Signs and Physical Evaluations .......................................................................................... 25 
9.8. 
Concomitant Medications ........................................................................................................... 25 
10. REPORTING CONVENTIONS ....................................................................................................... 26 
11. TECHNICAL DETAILS ................................................................................................................... 27 
12. SUMMARY OF CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED ANALYSES28 
13. REFERENCES .................................................................................................................................. 29 
14. APPENDICES ................................................................................................................................... 30 
 
TABLE MOCK-UPS ........................................................................................... 31 
 
FIGURE MOCK-UPS ........................................................................................ 145 
 
LISTINGS MOCK-UPS .................................................................................... 163 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
 
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LIST OF ABBREVIATIONS 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
BP 
Blood Pressure  
C 
Celsius 
CI 
Confidence Interval 
Cr 
Creatinine 
CRF 
Case Report Form 
CSR 
Clinical Study Report 
DMID 
Division of Microbiology and Infectious Diseases 
DSMB 
Data and Safety Monitoring Board 
eCRF 
Electronic Case Report Form 
F 
Fahrenheit 
FDA 
U.S. Food and Drug Administration 
GMT 
Geometric Mean Titer 
GSK 
GlaxoSmithKline 
HAI 
hemagglutination inhibition antibody 
Hgb 
Hemoglobin 
HHS 
U.S. Department of Health and Human Services 
ICH 
International Conference on Harmonisation 
IIV 
Inactivated Influenza Vaccine 
IM 
Intramuscularly 
IRB 
Institutional Review Board 
L 
Liter 
MAAE 
Medically Attended Adverse Event 
mcg 
Microgram 
MedDRA 
Medical Dictionary for Regulatory Activities  
mg 
Milligram 
mITT 
Modified Intention to Treat 
N, n 
Number  
NA 
neuraminidase 
Neut 
Neutralizing Antibody 


Statistical Analysis Plan - DMID Protocol: 17-0077 
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LIST OF ABBREVIATIONS (continued) 
 
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NIH 
National Institutes of Health 
NOCMC 
New Onset Chronic Medical Condition 
PIMMC 
Potentially Immune Mediated Medical Condition 
PP 
Per Protocol 
PLT 
Platelets 
PT 
Preferred Term 
RCD 
Reverse Cumulative Distribution  
SAE 
Serious Adverse Event 
SD 
Standard Deviation 
SDCC 
Statistical and Data Coordinating Center 
SMC 
Safety Monitoring Committee 
SOC  
System Organ Class 
T. Bili 
Total Bilirubin 
WBC 
White Blood Cell 
WHO 
World Health Organization 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
 
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1. 
PREFACE 
This Statistical Analysis Plan (SAP) for DMID Protocol 17-0077, “A Phase II Study in 
Healthy Adults (19-64 Years of Age) to Assess the Safety, Reactogenicity and 
Immunogenicity of Sequential or Simultaneous Intramuscular Administration of an AS03-
adjuvanted A/H7N9 Inactivated Influenza Vaccine with Seasonal Influenza Vaccine,” 
describes and expands upon the statistical information presented in the protocol.  
This document describes all planned analyses and provides reasons and justifications for 
these analyses. It also includes sample tables, figures, listings (TFLs) planned for (1) final 
analyses included in the preliminary report, and (2) analyses included in the Clinical Study 
Report (CSR). Regarding the final analyses and CSR, this SAP follows the International 
Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use (ICH) Guidelines, as indicated in Topic E3 (Structure and 
Content of Clinical Study Reports), and more generally is consistent with Topic E8 (General 
Considerations for Clinical Trials) and Topic E9 (Statistical Principles for Clinical Trials). 
The structure and content of the SAP provides sufficient detail to meet the requirements 
identified by the FDA and ICH, while all work planned and reported for this SAP will follow 
internationally accepted guidelines published by the American Statistical Association and the 
Royal Statistical Society for statistical practice.  
This document contains four sections: (1) a review of the study design, (2) general statistical 
considerations, (3) comprehensive statistical analysis methods for immunogenicity and safety 
outcomes, and (4) a list of proposed tables, figures and listings (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 A/H7N9 outbreaks in October 2016, more human cases of A/H7N9 infection have 
been reported in China than any prior A/H7N9 epidemic wave [3]. The U.S. Department of 
Health and Human Services (HHS) recently assessed A/H7N9 influenza virus as having a 
significant potential to cause a pandemic, and the greatest risk of causing severe disease. As a 
result, HHS has supported the production of fifth wave A/H7N9 inactivated influenza 9 
vaccines (IIVs) for the U.S. stockpile and for an assessment of their safety and 
immunogenicity in clinical trials. 
The goal of this clinical trial is to assess in healthy adults the safety, reactogenicity, and 
immunogenicity of two doses of AS03-adjuvanted 2017 A/H7N9 inactivated influenza 
vaccine (IIV) administered simultaneously (Group 1) or sequentially (Group 2) with seasonal 
influenza vaccine (IIV4), and to assess potential interference with the immunogenicity of 
either vaccine. A comparator group will receive IIV4 only at baseline (Group 3). The two 
doses of the A/H7N9 vaccine given with AS03 adjuvant will be administered approximately 
21 days apart.  
2.1. 
Purpose of the Analyses 
These analyses will assess the safety and immunogenicity of two doses of AS03-adjuvanted 
2017 A/H7N9 IIV administered sequentially or simultaneously with seasonal influenza 
vaccine and will be included in the clinical study report.  


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3. 
STUDY OBJECTIVES AND ENDPOINTS 
3.1. 
Study Objectives 
3.1.1. 
Primary 
Safety: 
• To assess the safety and reactogenicity following sequential or simultaneous 
intramuscular (IM) administration of 2 doses of AS03-adjuvanted 2017 A/H7N9 IIV 
and one dose of seasonal influenza vaccine (IIV4).  
Immunogenicity: 
• To assess the serum hemagglutination inhibition (HAI) and neutralizing (Neut) 
antibody responses against A/H7N9 at approximately 21 days following receipt of 
two doses of AS03-adjuvanted 2017 H7N9 IIV administered IM approximately 21 
days apart. 
• To assess the serum HAI and Neut antibody responses against the seasonal influenza 
strains at approximately 21 days following receipt of IIV4. 
3.1.2. 
Secondary  
Safety: 
• To assess unsolicited non-serious adverse events following sequential or 
simultaneous IM administration of AS03-adjuvanted 2017 A/H7N9 IIV and seasonal 
influenza vaccine (IIV4). 
• To assess medically attended adverse events (MAAEs), including new onset chronic 
medical conditions (NOCMCs) and potentially immune mediated conditions 
(PIMMCs), following sequential or simultaneous IM administration of AS03-
adjuvanted 2017 A/H7N9 IIV and IIV4. 
Immunogenicity: 
• To assess the HAI and Neut antibody responses at 21 days following receipt of 1 dose 
of AS03-adjuvanted 2017 A/H7N9 IIV. 
3.1.3. 
Exploratory 
Immunogenicity: 
• To assess the effects of age, sex, BMI, and receipt of prior year(s) seasonal influenza 
vaccine(s) on serum HAI antibody responses following receipt of two doses of AS03-
adjuvanted 2017 A/H7N9 IIV.  


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• To assess the durability of the antibody response to the 2017 A/H7N9 study vaccine 
strain and the IIV4 strains at approximately 180 days following the second dose of 
AS03-adjuvanted 2017 A/H7N9 IIV vaccine.  
• To assess the neuraminidase (NA) content of the 2017 H7N9 IIV and the licensed 
seasonal IIV4 and determine the serum antibody responses to NA following receipt of 
2017 H7N9 IIV. Note: analysis plans for this objective will be described in an 
addendum to this SAP once the NA assay has been selected. 
3.2. 
Endpoints 
3.2.1. 
Primary 
Safety: 
• 
Occurrence of all serious adverse events (SAEs) following the first study vaccination 
through approximately 12 months after the last study vaccination. 
• 
Occurrence of study vaccine-related SAEs following the first study vaccination 
through approximately 12 months after the last study vaccination. 
• 
Occurrence of solicited injection site and systemic adverse events (AEs) following 
each study vaccination through 7 days after each study vaccination. 
• 
Occurrence of clinical safety laboratory AEs following each study vaccination 
through approximately 7 days after each study vaccination. 
Immunogenicity: 
• For HAI and Neut antibodies, percentage of subjects achieving seroconversion 
against the 2017 H7N9 study vaccine strain (defined as either a pre-vaccination titer 
<1:10 and a post-vaccination titer ≥1:40 or a pre-vaccination titer ≥1:10 and a 
minimum four-fold rise in post-vaccination antibody titer) at approximately 21 days 
after 2 doses of AS03-adjuvanted 2017 H7N9 IIV (Group 1– Day 43; Group 2 – Day 
64; Group 3 – N/A). 
• 
For HAI and Neut antibodies, percentage of subjects achieving seroconversion 
against each of the study IIV4 strains at approximately 21 days after receipt of study 
IIV4 (Groups 1, 2 and 3 – Day 22).  
• For HAI and Neut antibodies, percentage of subjects with an antibody titer of ≥1:40 
against the influenza 2017 H7N9 study vaccine strain at approximately 21 days 
following receipt of 2 doses of AS03-adjuvanted 2017 H7N9 IIV (Group 1 – Day 43; 
Groups 2 – Day 64; Group 3 – N/A). 
• 
For HAI and Neut antibodies, percentage of subjects with an antibody titer of ≥1:40 
against each of the study IIV4 strains at approximately 21 days after receipt of study 
IIV4 (Groups 1, 2 and 3 – Day 22).  


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• GMTs of serum HAI and Neut antibodies against the 2017 H7N9 IIV strain at 
approximately 21 days following receipt of 2 doses of AS03-adjuvanted 2017 H7N9 
IIV (Group 1– Day 43; Group 2 – Day 64; Group 3 – N/A).  
• GMTs of serum HAI and Neut antibodies against each of the 2017 IIV4 strains at 
approximately 21 days after receipt of IIV4 (Group 1, 2 and 3– Day 22). 
3.2.2. 
Secondary 
Safety: 
• 
Occurrence of study vaccine-related unsolicited non-serious AEs following each 
study vaccination through approximately 21 days after each study vaccination. 
• 
Occurrence of all unsolicited non-SAEs following each study vaccination through 
approximately 21 days after each study vaccination.  
• 
Occurrence of MAAEs, including NOCMCs and PIMMCs, following the first study 
vaccination through approximately 12 months after the last study vaccination. 
Immunogenicity: 
• 
For HAI and Neut antibodies, percentage of subjects achieving seroconversion 
against the 2017 H7N9 vaccine strain at approximately 21 days after receipt of 1 dose 
of AS03-adjuvanted 2017 H7N9 IIV (Group 1– Day 22; Group 2 – Day 43; Group 3 
– N/A). 
• 
For HAI and Neut antibodies, percentage of subjects achieving serum HAI and Neut 
antibody titers ≥1:40 against the influenza 2017 H7N9 vaccine strain at baseline and 
approximately 21 days after receipt of 1 dose of AS03-adjuvanted 2017 H7N9 IIV 
(Group 1–Day 1 (baseline) and Day 22; Group 2 –Day 22 (baseline) and Day 43; 
Group 3 – N/A). 
• 
GMTs of serum HAI and Neut antibodies against the influenza 2017 H7N9 vaccine 
virus at baseline and at approximately 21 days after receipt of 1 dose of AS03-
adjuvanted 2017 H7N9 IIV. (Group 1–Day 1 (baseline) and Day 22; Group 2 –Day 
22 (baseline) and Day 43; Group 3 – N/A). 
3.2.3. 
Exploratory 
Immunogenicity: 
• For HAI and Neut antibodies, percentage of subjects achieving seroconversion, 
percentage with titer ≥1:40 and the GMTs against the 2017 H7N9 study vaccine 
strain approximately 21 and 180 days after 2 doses of adjuvanted 2017 H7N9 IIV, 
stratified by age, sex, BMI, and prior receipt of seasonal influenza vaccine(s) for 
Groups 1 and 2. 


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• For HAI and Neut antibodies, percentage of subjects achieving seroconversion, 
percentage with a titer ≥1:40 and the GMTs against the IIV4 vaccine strains 
approximately 21 and 180 days after receipt of IIV4, stratified by age, sex, BMI, and 
prior receipt of seasonal influenza vaccine(s). 
• For HAI and Neut antibodies, percentage of subjects achieving seroconversion, 
percentage with titer ≥1:40, and GMTs against the 2017 H7N9 study vaccine strain at 
approximately 180 days after 2 doses of adjuvanted 2017 H7N9 IIV for Groups 1  
and 2. 
• Percentage of subjects with detectable levels of serum N1, N2 and N9 NA-specific 
antibody elicited by 2017 H7N9 and seasonal IIV4 vaccination, and the correlation of 
the NA content of 2017 H7N9 IIV and seasonal IIV4 with the elicited NA specific 
antibody responses at baseline and approximately 21 and 180 days after 2 doses of 
adjuvanted 2017 H7N9 IIV for Groups 1 and 2; and approximately 21 and 180 days 
after receipt of the seasonal IIV4 vaccine for all Groups. Note: analysis plans for this 
endpoint will be described in an addendum to this SAP once the NA assay has been 
selected 
3.3. 
Study Definitions and Derived Variables 
For individual subjects, fold rise will be calculated as the ratio of: 
𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝−𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡
𝑝𝑝𝑝𝑝𝑝𝑝−𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑡𝑡𝑡𝑡𝑡𝑡𝑒𝑒𝑟𝑟, where 
pre-vaccination value is always the result obtained at Day 0, prior to the priming dose. 
HAI Seroconversion is defined as either a pre-vaccination HAI titer <10 and a post-
vaccination HAI titer ≥40 or a pre-vaccination HAI titer ≥10 and a minimum four-fold rise in 
post-vaccination HAI titer [5]. 
Neut Seroconversion is defined as either a pre-vaccination Neut titer <1:10 and a post-
vaccination Neut titer ≥1:40 or a pre-vaccination Neut titer ≥1:10 and a minimum four-fold 
rise in post-vaccination Neut antibody titer. 


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4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design and Plan 
DMID Protocol 17-0077 follows a Phase II randomized, open-label study design enrolling 
males and non-pregnant females aged 19-64 years who are in good health as determined by 
medical history and physical examination, and meet all eligibility criteria, including 
erythrocyte sedimentation rate (ESR) and negative urine or serum pregnancy test (for 
females). This clinical trial is designed to assess the safety, reactogenicity, and 
immunogenicity of a pre-pandemic AS03 (GSK) adjuvanted 2017 monovalent inactivated 
influenza A/H7N9 vaccine (2017 H7N9 IIV) manufactured by Sanofi Pasteur (3.75 mcg of 
HA per dose), when two doses are administered 21 days apart either sequentially or 
simultaneously (within 15 minutes) with licensed seasonal influenza vaccine.   
Subjects will be randomly assigned to 1 of 3 study groups with allocation 2:2:1 (see Table 1). 
All study doses will be administered IM approximately 21 days apart. Subjects assigned to 
treatment group 1 will receive seasonal IIV4 and AS03 adjuvanted 2017 H7N9 IIV 
concurrently at the first dose, and will return after approximately 21 days to receive a second 
dose of AS03 adjuvanted 2017 H7N9 IIV. Subjects assigned to treatment group 2 will 
receive seasonal IIV4 at the first dose followed by two doses at 21 and 42 days post IIV4 of 
AS03 adjuvanted 2017 H7N9 IIV. Subjects assigned to treatment group 3 will receive a 
single dose of IIV4. 
Reactogenicity will be measured by the occurrence of solicited injection site and systemic 
reactions from the time of each study vaccination through 7 days after each study 
vaccination. Unsolicited non-serious AEs will be collected from the time of each study 
vaccination through approximately 21 days after each study vaccination. SAEs and MAAEs, 
including NOCMCs and PIMMCs, will be collected from the time of the first study 
vaccination through approximately 12 months after the last study vaccination. Clinical 
laboratory evaluations for safety will be performed on venous blood collected prior to each 
study vaccination and approximately 7 days after each study vaccination. 
Immunogenicity testing will include performing HAI and Neut antibody assays against the 
2017 H7N9 vaccine virus on serum samples collected for Group 1 on Days 1 (baseline), 22, 
and 43, and at approximately 180 days post second adjuvanted 2017 H7N9 IIV dose (Day 
202), and for Group 2 on Study Days 22 (baseline), 43, and 64, and at approximately 180 
days post second 2017 H7N9 IIV adjuvanted dose (Day 223).Serological antibody assays 
will be performed against the vaccine viruses in IIV4 from serum samples collected at 
baseline (Day 1) and approximately 21 and 180 days following receipt of seasonal IIV4 
(Groups 1, 2, and 3).   
Novel methods for identifying and assessing alternative correlates of protection against 
influenza infection are needed.  To assess the NA-specific antibody response to vaccination, 
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under development.  If successful, the NA content in a dosage-specific manner can be 
correlated to the N9 NA-specific antibody responses elicited by the 2017 H7N9 IIV. 
4.2. 
Discussion of Study Design, Including the Choice of Control 
Groups 
This study uses a dose comparison concurrent control design. All subjects receive seasonal 
IIV4 vaccine either alone or administered simultaneously or sequentially with two doses of 
AS03 adjuvanted 2017 A/H7N9 IIV. 
4.3. 
Selection of Study Population 
The study population for this clinical trial is 150 males and non-pregnant females, 19-64 
years old, who are in good health and meet all eligibility criteria. The subjects will be 
recruited from the general population at the participating Vaccine Trial and Evaluation Unit 
(VTEU) sites that have substantial experience conducting large influenza vaccine studies. 
4.4. 
Treatments 
4.4.1. 
Treatments Administered  
Seasonal IIV4 will be administered to all enrolled subjects. The 2017 A/H7N9 Vaccine with 
AS03 Adjuvant will be administered to subjects in treatment groups 1 and 2. 
4.4.2. 
Identity of Investigational Product 
See the study protocol for details of study product formulation. 
4.4.3. 
Method of Assigning Subjects to Treatment Groups 
(Randomization) 
Enrollment/randomization will be performed through the enrollment module in the electronic 
data capture system maintained by the Statistical and Data Coordinating Center (SDCC).  
Eligible subjects will be stratified by clinical site and randomly assigned with allocation 
(2:2:1) to 1 of 3 treatment groups indicated in Table 1. The treatment sequence was generated 
using permuted block randomization to provide an approximately balanced allocation to the 
treatment groups during the study. 
4.4.4. 
Selection of Doses in the Study 
Participants in this study are to receive one dose of seasonal IIV4 (all subjects), as well as 
two doses of AS03 adjuvanted 2017 A/H7N9 at HA dose of 3.75 mcg (treatment groups 1 
and 2). The 3.75 mcg with AS03 dose was selected to evaluate safety and immunogenicity of 
antigen sparing dose strategies. 


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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 number and 
timing of AS03 adjuvanted 2017 A/H7N9 vaccinations. The first dose takes place on the day 
of randomization and will include vaccination with IIV4 for all subjects. Subjects in Group 1 
will also receive the first A/H7N9 vaccination at the randomization visit. The second dose, a 
single A/H7N9 vaccination, if applicable, takes place approximately 21 days after the first 
dose (protocol defined window of 21-28 days post first dose). The third dose, a single 
A/H7N9 vaccination, if applicable, takes place approximately 21 days after the second dose 
(protocol defined window of 21-28 days post second dose). 
4.4.6. 
Blinding 
This trial is open-label. Subjects, investigators, and study personnel performing any study-
related assessments following study vaccine administration are not blinded to study 
treatment. However, laboratory personnel performing HAI and Neut antibody assays will 
receive serum samples blinded to subject ID number and sample visit number. 
The randomization scheme was generated by the SDCC and each subject’s treatment 
assignment is displayed in AdvantageEDC upon enrollment. 
The Data and Safety Monitoring Board (DSMB) may receive data in aggregate and presented 
by treatment group, including expected and observed rates of the expected AEs. The DSMB 
will review grouped data in the closed session only. 
4.4.7. 
Prior and Concomitant Therapy 
Administration of any medications, therapies, or vaccines (including prescription and over-
the-counter drugs as well as herbals, vitamins, and supplements) from 60 days prior to study 
vaccination through 21 days post final dose will be solicited from the participant during 
screening, enrollment, and follow-up. Any reported prior therapies from up to 30 days prior 
to vaccination through 21 days post final dose will be recorded in the appropriate data 
collection form.  
Use of concomitant medications is allowed prior to and during the trial with the exception of 
medications and therapies that might interfere with the evaluation of the investigational 
product. Medications in this category include the prohibited medication per the Subject 
Exclusion Criteria (protocol Section 5.1.2). In addition, the site principal investigator or 
appropriate sub-investigator may identify other medications that should not be used due to a 
risk to subject safety or assessment of reactogenicity and immunogenicity. 
4.4.8. 
Treatment Compliance 
All subjects are to receive one dose of seasonal IIV4 and subjects in treatment groups 1 and 2 
are to receive two doses of AS03 adjuvanted 2017 A/H7N9 IIV vaccine administered in the 
clinic based on study group assignment. 


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4.5. 
Immunogenicity and Safety Variables 
See Table 2, Table 3, Table 4, Table 5, Table 6, and Table 7 for schedules of study 
procedures by treatment group. 
4.5.1. 
Safety Variables 
Safety will be assessed by the frequency and severity of: 
1. SAEs occurring from the time of the first study vaccination through approximately 12 
months after the last study vaccination. 
2. Solicited AEs – reactogenicity events occurring from the time of each study 
vaccination through 7 days after each study vaccination: 
a) Injection site reactions including pruritus, ecchymosis, erythema, induration 
(hardness)/edema (swelling), pain, and tenderness. 
b) Systemic reactions including fever, feverishness, fatigue, malaise, myalgia, 
arthralgia, headache, and nausea. 
3. Clinical safety laboratory AEs occurring from the time of each study vaccination 
through approximately 7 days after each study vaccination. Parameters to be 
evaluated include white blood cells (WBC), hemoglobin (Hgb), platelets (PLT), 
alanine aminotransferase (ALT), total bilirubin (T. Bili), and creatinine (Cr). 
4. Unsolicited AEs – non-serious AEs occurring from the time of each study vaccination 
through approximately 21 days after each study vaccination. 
5. MAAEs, including NOCMCs, and PIMMCs occurring from the time of the first study 
vaccination through approximately 12 months after the last study vaccination. 
Grading scales for injection site and systemic solicited reactions, vital signs, and clinical 
laboratory parameters are provided in Table 13, Table 14, Table 15, and Table 16. 
4.5.2. 
Immunogenicity Variables 
Individual HAI and Neut results will be reported by the central immunology laboratory for 
the homologous 2017 A/H7N9 vaccine strain, A/Hong Kong/125/2017, the homologous 
strains in the seasonal 2017/2018 IIV4 Fluzone vaccine (A/Michigan/45/2015 X-275 
(H1N1), A/Hong Kong/4801/2014 X263B(H3N2), B/Phuket/3073/2013 (B Yamagata 
lineage), and B/Brisbane/60/2008 (B Victoria lineage)). Assay results are reported as a 
reciprocal titer with values of 10*2k, where k=0, 1, 2, etc. The lower limit of detection for the 
HAI and Neut assays is 1:10; values below the limit of detection are reported as ‘<10’, and 
for analysis are imputed 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. 


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The assay to determine the influenza virus N9 Neuraminidase (NA) antibody response to 
vaccination is under development. An addendum to the SAP will be generated to outline the 
planned analyses when assay development is complete.  
For subjects in Group 1 (Simultaneous Administration) there is potential for an overlap 
between the windows for Visit 9 (Day 181 post vaccination 1 ±14 days) and Visit 10 (Day 
181 post vaccination 2 ±14 days). Should a subject complete both visits on the same date, 
HAI and Neut results against the seasonal IIV4 vaccine strains on that date will be associated 
with Visit 9, while HAI and Neut results against the 2017 H7N9 vaccine strain on that date 
will be associated with Visit 10. 
All immunogenicity data will be uploaded into the SDCC’s electronic data capture system. 


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5. 
SAMPLE SIZE CONSIDERATIONS 
This study is planned to enroll a minimum of 60 subjects in Groups 1-2, and 30 subjects in 
Group 3. This 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 and to uncover 
any safety issues that occur at a sufficiently high rate that they might be observed in a study 
of this size. As such, the type one error rate, alpha = 0.05, is not adjusted for multiple 
comparisons. 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 8 indicates the probability of observing one or more safety events, such as solicited 
injection site or systemic reactogenicity events or an unsolicited non-serious AE of a 
particular type for a single treatment group (N = 30 or 60), and for all subjects receiving 
AS03-adjuvanted 2017 H7N9 IIV (N = 120). 
Binomial confidence intervals (CI) are widest (have the least precision) when the response 
rate is 50%. Table 9 is presented to indicate the worst case scenario for precision of observed 
exact (Clopper-Pearson) binomial confidence intervals. 
For each of the primary immunogenicity objective, a power analysis is provided below for 
testing the following hypotheses with the planned sample size, where pc = proportion 
responders in comparator arm; pe = proportion responders in experimental arm. 
Test for difference in proportion responders: 
H0: pc – pe = 0 – No difference in proportion responders 
H1: pc – pe ≠ 0 – difference in response rates 
Primary Immunogenicity Objective 1: Evaluate antibody responses against A/H7N9 at 
approximately 21 days following receipt of two doses of AS03-adjuvanted 2017 H7N9 IIV. 
Comparison between simultaneous and sequential receipt to IIV4, i.e., Group 1 at Day 43 vs. 
Group 2 at Day 64. 
Primary Immunogenicity Objective 2: Evaluate antibody responses against the seasonal 
influenza strains at approximately 21 days following receipt of IIV4. 
Comparator Group (N = 75):   
• Group 2 (IIV4/H7N9/H7N9) + Group 3 (IIV4) at Day 22  
Experimental Groups (N = 50/group): 
• Group 1 (IIV4+H7N9 /H7N9) at Day 64 
Table 10 and Table 11 illustrate the minimum detectable differences in the proportion of 
subjects responding (e.g., attaining seroconversion or a titer ≥1:40) between two treatment 
groups using a two-sided Likelihood Ratio Test and alpha = 0.05. 


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6. 
GENERAL STATISTICAL CONSIDERATIONS 
6.1. 
General Principles 
All continuous variables will be summarized using the following descriptive statistics: n 
(non-missing sample size), mean, standard deviation, median, maximum and minimum. The 
frequency and percentages (based on the non-missing sample size) of observed levels will be 
reported for all categorical measures. In general, all data will be listed, sorted by site, 
treatment and subject, and when appropriate by visit number within subject. All summary 
tables will be structured with a column for each treatment group in the following order: 
• Group 1: Simultaneous Administration (D1: IIV4/H7N9; D22: H7N9) 
• Group 2: Sequential Administration (D1: IIV4; D22: H7N9; D43: H7N9) 
• Group 3: IIV4 Only (D1: IIV4) 
All tables will be annotated with the total population size relevant to that table/treatment, 
including any missing observations. 
6.2. 
Timing of Analyses 
6.2.1. 
Preliminary Report and CSR 
Clinical, safety, and reactogenicity data through Day 64 will represent the primary clinical 
database for this trial. Once the last subject completes the Day 64 visit, the primary clinical 
database will be cleaned, monitored, and locked. Analyses of safety, reactogenicity, and 
available immunogenicity (HAI and Neut antibody assays through day 64) data by treatment 
arm are planned. A preliminary report will be prepared by the SDCC after the primary 
clinical database is locked and all HAI and Neut data through 21 days after the last study 
vaccination are received. Immunogenicity and safety analyses will be presented in aggregate 
by treatment group; individual subject data will not be presented in the preliminary report. 
These analyses may be made available to the sponsor for planning subsequent trials and to 
the lead principal investigator for publication. These analyses will not be used to make any 
decisions concerning the conduct of this trial. All analyses of data included in the preliminary 
report for early release will be considered the final analysis of these data, and also included 
in the final CSR.  
Tables and figures to be included in the Preliminary Report are indicated with the symbol * 
in the title. 
Analysis of exploratory immunogenicity endpoints may be performed and released as the 
data are available from the research laboratory. Any such analyses would be considered the 
final analysis for the endpoint, and included in the CSR.  
The final CSR will be completed after the last subject’s last visit is completed, and the final 
clinical database including all long-term safety follow-up data is cleaned, monitored and 


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locked. Additional exploratory immunogenicity endpoint data not available at the time of 
CSR preparation may be included in an addendum to the CSR. 
6.3. 
Analysis Populations 
6.3.1. 
Safety Population 
The Safety Analysis population includes all subjects who received at least one study 
vaccination. 
6.3.2. 
Modified Intention-to-Treat (mITT) Population 
The modified intent-to-treat (mITT) population includes all subjects who received at least 
one dose of study vaccine and contributed both pre- and at least one post-study vaccination 
venous blood samples for immunogenicity testing (HAI or Neut antibody assays) for which 
valid results were reported. For analyses using the mITT population, subjects in Group 2 who 
discontinue treatment after receiving the single IIV4 dose (Dose 1) but prior to receiving the 
first dose of the H7N9 vaccine (Dose 2) will be analyzed with group 3. All other subjects will 
be grouped based on randomized treatment group. 
6.3.3. 
Per Protocol Population 
The per protocol (PP) population includes all subjects in the mITT subset with the following 
exclusions: 
• Data from all available visits for subjects found to be ineligible at baseline. 
• Data from all visits subsequent to major protocol deviations, such as: 
o Second or third dose not received, 
o Second or third dose received out of window, 
o Receipt of non-study licensed live vaccine within 30 days before or after each study 
vaccination, 
o Receipt of non-study licensed inactivated vaccine within 14 days before or after 
each study vaccination, 
o Receipt of immunosuppressive therapy (e.g., corticosteroids) within 30 days before 
or after each study vaccination. 
• Data from any visit that occurs out of window by more than one day. 
For analyses using the PP population, subjects will be grouped based on study vaccinations 
received - subjects in Group 2 who discontinue treatment after receiving the single IIV4 dose 
(Dose 1) but prior to receiving the first dose of the H7N9 vaccine (Dose 2) will be analyzed 
with Group 3. 


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6.4. 
Covariates and Subgroups 
As a protocol defined exploratory analysis, HAI antibody response following the second 
vaccination will be summarized stratified by the following covariates: age (categorical: 19-
34, 35-49, 50-64), sex (male, female), body mass index (<30, ≥30), and prior receipt of 
seasonal influenza vaccine(s) (received 2016-2017, did not receive 2016-2017, unknown), 
and these covariates will be considered in statistical modeling as described in Section 8.3. As 
these analyses are exploratory the study was not powered for any subgroup analyses.  
6.5. 
Missing Data 
All attempts will be made to collect all data per protocol. As missing data are expected to be 
minimal, no imputation will be performed for missing values. Any data point that appears to 
be erroneous or inexplicable based on clinical judgment will be investigated as a possible 
outlier. If data points are identified as outliers, sensitivity analyses will be performed to 
examine the impact of including or excluding the outliers. Any substantive differences in 
these analyses will be reported. 
6.6. 
Interim Analyses and Data Monitoring 
Interim analyses will only be used to terminate this trial in the event that unanticipated safety 
events deemed to be of sufficient concern require such action by the sponsor. These 
assessments will not be made on the basis of testing a formal statistical hypothesis; therefore, 
p-value adjustment will not be made to any analyses. A DSMB will be convened by DMID 
to review study progress and participant, clinical, safety, and reactogenicity and 
immunogenicity data. 
A preliminary report of safety and immunogenicity data through Day 64 will be prepared as 
described in section protocol section 11.6; though this report will be released while subjects 
remain in the trial for long-term safety and immunogenicity follow-up, it will be considered 
the final analysis of these data. 
Emergent public health needs may dictate additional interim safety, reactogenicity, and/or 
immunogenicity analyses be performed on available information at any time during the trial. 
If this occurs, immunogenicity data will be analyzed as results are available from the central 
immunogenicity laboratory. 
6.6.1. 
Interim Safety Review 
An interim safety review may include enrollment and demographic information, medical 
history, concomitant medications, physical assessments, clinical laboratory values, dosing 
compliance, and solicited and unsolicited AE/SAEs. Additional data may be requested by the 
DSMB, and interim statistical reports may be generated as deemed necessary and appropriate 
by DMID. The DSMB may receive data in aggregate and presented by treatment group. The 
DSMB may also be provided with expected and observed rates of the expected AEs by 


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treatment group, and may request the treatment assignment for an individual subject if 
required for safety assessment. The DSMB will review data grouped by treatment group 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 
No interim immunogenicity analysis is planned. Should emergent public health needs dictate 
immunogenicity review, immune responses will be summarized in terms of strain-specific 
2017 A/H7N9 and IIV4 HAI and Neut antibody titers for subjects that receive sequential or 
simultaneous administration of AS03-adjuvanted 2017 H7N9 IIV and seasonal IIV4. It is 
anticipated that all analyses will be carried out in parallel for both assays, but reports may be 
prepared separately for HAI and Neuts if results are available on different timelines. Interim 
analyses will focus on rates of titers ≥1:40, seroconversion (see definition in Section 3.3) 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 
and Clinical Project manager, and the DSMB. Reports will include data summarized by 
treatment group. 
6.7. 
Multicenter Studies 
Randomization was stratified by site, but data will be pooled across all clinical sites for all 
analyses. Center effects are not anticipated because the sites use standardized procedures for 
vaccination and assessment of solicited and unsolicited AEs, and the study relies on a central 
laboratory for immunogenicity assessments. 
6.8. 
Multiple Comparisons/Multiplicity 
This study was designed to obtain preliminary estimates of safety and immune response to 
A/H7N9 and IIV4 vaccination in healthy adults. The study was not designed to test any 
specific null hypothesis, and as such no adjustment for multiple comparisons will be 
performed. 


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7. 
STUDY SUBJECTS 
7.1. 
Subject Disposition 
Table 17 will present a summary of the reasons that subjects were screened but not enrolled. 
The number and percentage of enrolled subjects excluded from each analysis population by 
treatment group are presented in Table 18. A listing of subjects excluded from each analysis 
population will be presented in Listing 5.  
The disposition of subjects in the study will be tabulated by treatment group (Table 19). The 
table will show the total number of subjects screened, randomized, receiving the first dose, 
receiving the second dose, receiving the third dose, completing the blood draw for the 
primary immunogenicity endpoints, and completing the last visit. 
A flowchart showing the disposition of study subjects, adapted from the CONSORT 
Statement [4] will be included and will present the number of subjects screened, randomized, 
lost to follow up, and analyzed, by treatment group (Figure 1). 
A listing of subjects who were discontinued from treatment or terminated from study follow-
up and the reason will be included in Listing 2.   
7.2. 
Protocol Deviations 
A summary of subject-specific protocol deviations will be presented by the deviation 
category and deviation type, and treatment group for all enrolled subjects (Table 12). Major 
deviations that will be reviewed for possible exclusion of immunogenicity results from the 
PP population include deviations related to eligibility/enrollment, treatment administration 
schedule, follow-up visit schedule, and receipt of exclusionary vaccines or medications. All 
subject-specific protocol deviations and non subject-specific protocol deviations will be 
included in Listing 3 and Listing 4. 


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8. 
IMMUNOGENICITY EVALUATION 
Immunogenicity data summaries and analysis for primary and secondary endpoints will be 
presented for the mITT and PP populations. Immune responses in terms of strain-specific 
A/H7N9 HAI and Neut antibody titers will be summarized by treatment 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 
≥1:40, percentage of subjects achieving seroconversion, and GMTs along with corresponding 
95% CI. Exact confidence intervals will be presented for proportional endpoints. Summaries 
of primary and secondary immunogenicity endpoints are presented for the 2017 H7N9 strain 
in Table 28, Table 29, Table 30, and Table 31 and for the seasonal IIV4 strain in Table 32, 
Table 33, Table 34, and Table 35.  
Reverse cumulative distribution (RCD) curves will be presented for post-vaccination HAI 
and Neut antibody titers. Plots for each assay will be generated with 5 panels (21 days post 
dose 1, 21 days post dose 2, 21 days post dose 3, 180 days post dose 1, and 180 days post 
final dose), and separate curves within each panel for each treatment group, as shown in 
Figure 2, Figure 3, Figure 4, and Figure 5 for the 2017 A/H7N9 strain. RCD curves for the 
IIV4 strains will be presented as in Figure 6 , Figure 7 , Figure 8, Figure 9, Figure 10, 
Figure 11, Figure 12, Figure 13, Figure 14, Figure 15, Figure 16, Figure 17, Figure 18, 
Figure 19, Figure 20, and Figure 21. 
Figures depicting the HAI and Neut GMT over time will also be presented as shown in 
Figure 22, Figure 23, Figure 24, and Figure 25 for the 2017 A/H7N9 strain, and for the IIV4 
strains in Figure 26, Figure 27, Figure 28, Figure 29, Figure 30, Figure 31, Figure 32, 
Figure 33, Figure 34, Figure 35, Figure 36, Figure 37, Figure 38, Figure 39, Figure 40, and 
Figure 41. 
The spearman correlation between HAI and Neut antibody titers will be calculated at each 
time point over all groups. The correlation will be depicted in scatter plots as Figure 42 and 
Figure 43 for the 2017 A/H7N9 strain. Scatterplots depicting correlation for the IIV4 strains 
will be created as Figure 44, Figure 45, Figure 46, Figure 47, Figure 48, Figure 49, Figure 50, 
and Figure 51. 
Individual HAI and Neut assay results will be provided in Listing 8. 
8.1. 
Primary Immunogenicity Analysis 
The primary immunogenicity endpoints HAI and Neut seroconversion, percentage of 
subjects with titer ≥1:40, and GMTs against the seasonal IIV4 strains 21 days after the IIV4 
vaccination for all groups and against the homologous A/H7N9 vaccine strain 21 days after 
the second dose of AS03 adjuvanted 2017 H7N9 IIV will be summarized as described above. 
The primary analysis population will be mITT, with results from the PP population providing 
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defined conditions. Regression modelling of seroconversion and log titers is planned as 
described in Section 8.3.2. 
8.2. 
Secondary Immunogenicity Analyses 
The secondary immunogenicity endpoints HAI and Neut seroconversion, percentage of 
subjects with titer >40, and GMTs against the homologous A/H7N9 vaccine strain 21 days 
after the first AS03-adjuvanted 2017 H7N9 vaccination will be summarized as described 
above. No formal hypothesis testing is planned. 
8.3. 
Exploratory Immunogenicity Analyses 
Immunogenicity data summaries and analysis for exploratory endpoints will be presented for 
the PP populations. 
8.3.1. 
Covariate Analysis 
As an exploratory analysis, seroconversion and GMT of serum antibody for both HAI and 
Neut against the homologous 2017 A/H7N9 strain at 21 and 180 days after the second dose 
of AS03 adjuvanted 2017 H7N9 IIV (treatment groups 1 and 2 only) will be summarized by 
treatment group stratified by age (categorized as those subjects ages 19-34, 34-49, and 50-64 
years) (Table 36, Table 37, Table 38, and Table 39), by sex (Table 44, Table 45, Table 46, 
and Table 47), by BMI (Table 52, Table 53, Table 54, and Table 55), and by prior receipt of 
the 2016-2017 seasonal influenza vaccine (Table 60, Table 61, Table 62, and Table 63). 
These analyses will be repeated for HAI and Neut titer results against each of the four IIV4 
vaccine strains at 21 and 180 days post receipt of seasonal IIV4 vaccine (by age category: 
Table 40, Table 41, Table 42, and Table 43; by sex: Table 48, Table 49, Table 50, and 
Table 51; by BMI: Table 56, Table 57, Table 58, and Table 59; by prior receipt of seasonal 
influenza vaccine: Table 64, Table 65, Table 66, and Table 67). 
The stratified summaries will be presented for the PP population. For the 2017 A/H7N9 
strain it is anticipated that subjects will have little to no pre-existing antibody at baseline, so 
seroconversion and titer ≥40 endpoints will be similar. 
8.3.2. 
Regression Modeling 
Logistic and multivariate linear regression will be utilized to test for the effects of the 
treatment schedule on seroconversion and GMT against the homologous 2017 A/H7N9 strain 
and against each of the seasonal IIV4 strains for the PP population. Similar models will be fit 
for HAI and Neut Antibodies for each strain and time point. Separate models will be fit for 
data from Day 21 post dose and Day 180 post dose.  
Logistic regression will be fit to examine the relationship of HAI or Neut seroconversion at 
21 or 180 days after the dose of interest (second dose of AS03 adjuvanted A/H7N9 IIV for 
the 2017 A/H7N9 strain; IIV4 vaccination for the seasonal IIV4 strains) with treatment 
schedule. If the available titer data meets the required assumptions of normality after log 


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transformation, multiple linear regression will be fit to examine the relationship of log 
transformed titers at 21 or 180 days after the dose of interest (second dose of AS03 
adjuvanted A/H7N9 IIV for the 2017 A/H7N9 strain; IIV4 vaccination for the seasonal IIV4 
strains) with treatment schedule. All models will be fit with and without adjustment for the 
following covariates (Z): age in years, sex (female, male), BMI (<30, ≥30), and prior receipt 
of seasonal influenza vaccine (did not receive 2016-2017 seasonal vaccine, received 2016-
2017 seasonal vaccine). The models as shown below assume a linear relationship between 
age in years and both probability of seroconversion and GMT. The validity of this 
assumption will be assessed prior to analysis and, if the relationship between age and 
response is found to be non-linear, adjustments will be made to model parameters to satisfy 
regression assumptions. 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 for the 
2017 A/H7N9 strain without covariate adjustment in Table 68, Table 69, Table 70, Table 71, 
and with covariate adjustment in Table 76, Table 77, Table 78, Table 79; and for the seasonal 
IIV4 strains without covariate adjustment in Table 72, Table 73, Table 74, Table 75, and with 
covariate adjustment in Table 80, Table 81, Table 82, Table 83. Parameter estimates for the 
multiple linear regression models will be presented for the 2017 A/H7N9 strain without 
covariate adjustment in Table 84, Table 85, Table 86, Table 87, and with covariate 
adjustment in Table 92, Table 93, Table 94, Table 95; and for the seasonal IIV4 strains 
without covariate adjustment in Table 88, Table 89, Table 90, Table 91, and with covariate 
adjustment in Table 96, Table 97, Table 98, Table 99. 
Model 1A: Logistic Regression (without covariate adjustment): 
𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙[𝑃𝑃(𝑠𝑠𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒𝑒)] = 𝛽𝛽0 + 𝛽𝛽1 × 𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇+ 𝜀𝜀 
Model 1B: Logistic Regression (with covariate adjustment): 
𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙[𝑃𝑃(𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠)] = 𝛽𝛽0 + 𝛽𝛽1 × 𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇+ 𝛽𝛽2 × 𝑍𝑍+ 𝜀𝜀 
Model 2A: Multiple Linear Regression (without covariate adjustment): 
𝑙𝑙𝑜𝑜𝑜𝑜(𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡) = 𝛽𝛽0 + 𝛽𝛽1 × 𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇+ 𝜀𝜀 
Model 2B: Multiple Linear Regression (with covariate adjustment): 
𝑙𝑙𝑙𝑙𝑙𝑙(𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡) = 𝛽𝛽0 + 𝛽𝛽1 × 𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇+ 𝛽𝛽2 × 𝑍𝑍+ 𝜀𝜀 
Subjects missing data for one or more covariates will be excluded from Models 1B and 2B. 
8.3.3. 
NA Serum Antibody Responses 
Descriptions of the NA assays and planned analyses will be described in an addendum to this 
SAP. 


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9. 
SAFETY EVALUATION 
All summaries and analysis of safety data will be presented for the Safety Analysis 
Population. Safety summaries will be presented overall and grouped by treatment group. 
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 will be reported for all categorical measures. The denominator for the percentages may 
be based on the number of non-missing observations for an assessment or based on the 
number of subjects in a population. This will be described for each table. 
9.1. 
Demographic and Other Baseline Characteristics 
Summaries of age, sex, ethnicity, race, BMI, and prior receipt of seasonal influenza vaccine 
will be presented by site (Table 23, Table 24) and by treatment group (Table 25, Table 26). 
Age will be summarized as a continuous variable. Ethnicity is categorized as Hispanic or 
Latino, or not Hispanic and not Latino. In accordance with NIH reporting policy, subjects 
may self-designate as belonging to more than one race or may refuse to identify a race, the 
latter reflected in the electronic case report form (eCRF) as “No” to each racial option. BMI 
will be summarized as a continuous as well as categorical variable, categorized as (<30, 
≥30). Self-reported history of prior receipt of seasonal influenza vaccine will be categorized 
as follows: received 2016-2017 seasonal vaccine, did not receive 2016-2017 seasonal 
vaccine, or unknown. Demographic information for individual subjects will be provided in 
Listing 6. Subjects’ prior influenza vaccination history (seasonal and non-seasonal) will be 
provided in Listing 8. 
9.1.1. 
Prior and Concurrent Illnesses and Medical Conditions 
All current illnesses and past or pre-existing medical conditions will be coded using Medical 
Dictionary for Regulatory Activities (MedDRA) version 20.0 or higher. 
Summaries of subjects’ prior and concurrent medical conditions will be presented by 
treatment group (Table 27). 
Individual subject listings will be presented for all reported medical history including prior 
and concurrent medical conditions (Listing 7). 
9.1.2. 
Prior and Concurrent Medications  
Concomitant medications will be coded to the Anatomical Therapeutic Classification using 
the WHO Drug Dictionary. The use of concomitant medications during the study will be 
summarized by ATC1 and ATC2 code and treatment group for the Safety population 
(Table 149). A listing of concomitant medications will be presented (Listing 17).  


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9.2. 
Measurements of Treatment Compliance 
All subjects are to receive IIV4 vaccine on Study Day 1. Subjects in Group 1 (Simultaneous 
Administration) will also receive the first dose of 2017 A/H7N9 in the contralateral arm on 
Study Day 1, with the second dose of 2017 A/H7N9 administered 21 days later (Study Day 
22). Subjects in Group 2 will have two doses of 2017 A/H7N9 vaccine administered 21 days 
apart (Study Days 22 and 43). Subjects in Group 3 will receive no further doses. The number 
of study vaccinations administered to subjects will be presented by treatment group and by 
site in Table 20, Table 21, Table 22, and as part of the subject disposition table (Table 19). 
Listing 1 presents subjects who received investigational product with randomized treatment 
group and study product received for each vaccination. 
9.3. 
Adverse Events 
A summary of all adverse events is provided in Table 100. A summary of those events that 
occurred in ≥5% of subjects in any treatment group is provided in Table 101. 
9.3.1. 
Solicited Events and Symptoms 
Systemic solicited adverse events were collected pre-vaccination, and systemic and local 
solicited adverse events were collected at-least 20 minutes post-vaccination and then daily 
for 7 days after each vaccination and graded on a scale of 0 (absent), 1 (mild), 2 (moderate) 
and 3 (severe). Systemic events include fever, feverishness, fatigue, malaise, myalgia, 
arthralgia, headache, and nausea. Local events include pruritus, ecchymosis, erythema, 
induration/swelling, pain, and tenderness. Ecchymosis, erythema, and induration are 
measured by both functional and measurement grading scales as defined in Table 13. The 
grading scale for systemic events, including quantitative grading for fever, is included in 
Table 14.  
When calculating the incidence of solicited events, each subject will be counted once at the 
highest severity following the applicable vaccination, and any repetitions will be ignored. For 
summaries presented separately for each vaccination, the denominator for percentages will be 
the number of subjects who received the respective vaccination with non-missing data for the 
event summarized. For summaries over all vaccinations the denominator will be the number 
of subjects who received at least one vaccination with non-missing data for the event 
summarized. 
The number and percentage of subjects reporting at least one solicited adverse event of each 
severity will be summarized for each solicited symptom, any systemic symptom, any local 
symptom, and any symptoms. For each event the denominator is the number of subjects who 
received the applicable vaccination with non-missing data for the specific event. The 95% CI 
calculated using Clopper-Pearson methodology from a binomial distribution (SAS Proc Freq 
with a binomial option) will be presented (Table 102, Table 103, Table 104, Table 105).  
Logistic regression models will be fit to estimate the effect of treatment schedule on the 


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probability of reporting any local event or reporting any systemic event (Table 106, 
Table 107). If statistically significant effects are observed in the model for local events or 
systemic events, then additional models will be fit for each individual event of that type. 
𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙[𝑃𝑃(𝐸𝐸𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣)] = 𝛽𝛽0 + 𝛽𝛽1 × 𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇+ 𝜀𝜀, 
For each systemic and local event, any systemic event, any local event, and any solicited 
event, the maximum severity over 7 days after each vaccination will be summarized for the 
Safety population. The number and percentage of subjects reporting each event will be 
summarized by the maximum severity and treatment group, separately for each dose and over 
all doses. For each event the denominator is the number of subjects who received the 
applicable vaccination with non-missing data for the specific event. The 95% CI calculated 
using Clopper-Pearson methodology from a binomial distribution (SAS Proc Freq with a 
binomial option) will be presented (Table 108, Table 109, Table 110, Table 111). 
The number of subjects reporting a solicited adverse event will be summarized for each day 
post vaccination for each vaccination and for all vaccinations combined both in a summary 
table (Table 112, Table 113, Table 114, Table 115) and graphically in a bar chart (Figure 52 
and Figure 53). A comparison of the event rate for each treatment group between study 
vaccinations will be presented for those groups receiving multiple vaccinations, including p-
values from McNemar’s test performed (Table 116, Table 117). 
Systemic and Local solicited events reported by subject will be presented in Listing 10 and 
Listing 11, sorted by subject ID, vaccination number, parameter, and study day. 
9.3.2. 
Unsolicited Adverse Events 
When calculating the incidence of unsolicited AEs (i.e., on a per subject basis), each subject 
will only be counted once at the highest severity and/or relationship, and any repetitions of 
AEs within a subject will be ignored; the denominator will be the total number of subjects in 
the safety population. All AEs reported will be included in the summaries and analyses. 
The number and percentage of subjects reporting at least one unsolicited AE will be 
summarized by MedDRA system organ class and preferred term. A 95% CI will be presented 
for the percentage of subjects reporting any unsolicited AE (serious or non-serious) for each 
MedDRA system organ class and preferred term over all study vaccinations (Table 118). 
The following summaries for unsolicited AEs will be presented by MedDRA system organ 
class, preferred term, and treatment group: 
• Incidence of AEs by severity and relationship to study product (Table 119); 
• Incidence of non-serious, related AEs by severity (Table 120); 
• Incidence of AEs over time (Days 1-8, Days 9-22 post each study vaccination) 
(Table 121); 


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• Incidence of non-serious, related AEs over time (Days 1-8, Days 9-22 post each study 
vaccination) (Table 122) – note this table presents results for secondary safety 
endpoint, “Occurrence of study vaccine-related unsolicited non-serious AEs from the 
time of each study vaccination through approximately 21 days after each study 
vaccination”; 
• Total frequency of AEs over time (Days 1-8, Days 9-22 post each study vaccination) 
(Table 123); 
• Subject listing of non-serious AEs of moderate or greater severity (Table 128);  
• Bar chart displaying total frequency of AEs by severity and MedDRA system organ 
class and treatment group (Figure 54); 
• Bar chart displaying incidence of AEs by severity and MedDRA system organ class, 
and treatment group (Figure 55); 
• Bar chart displaying total frequency and incidence of AEs by relationship to study 
product, MedDRA system organ class, and treatment group (Figure 56 and 
Figure 57). 
9.4. 
Deaths, Serious Adverse Events and other Significant Adverse 
Events 
The following listings will be presented including Subject ID, Age (years) AE Description, 
AE Onset Date/End Date, Last Vaccination Received/Days Post Vaccination, Reason 
Reported as an SAE, Relationship to Treatment, Alternate Etiology if not Related, Outcome, 
and Duration of Event (days): 
• Deaths and Serious Adverse Events (Table 124); 
• Medically Attended Adverse Events (Table 125); 
• Potentially Immune Mediated Medical Conditions (Table 126); 
• New Onset Chronic Medical Conditions (Table 127). 
A listing of all reported AEs by subject will be presented in Listing 12, sorted by Treatment 
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 18, Listing 19, Listing 20, Listing 21, and Listing 22 will present any study 
pregnancies and their outcomes. 


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9.6. 
Clinical Laboratory Evaluations 
Clinical safety laboratory parameters (WBC, Hgb, PLT, ALT, T. Bili, Cr) will be collected 
from each subject prior to each study vaccination and approximately 7 days after each study 
vaccination. These evaluations will be performed by the central clinical laboratory. The 
grading scale for clinical laboratory evaluations is presented in Table 16. Clinical laboratory 
evaluations assessed on Day 1 prior to the first study vaccination will be considered as 
baseline. 
The distribution of laboratory results by severity, study day and treatment group will be 
presented in Table 129, Table 130, Table 131, Table 132, Table 133, Table 134, and 
Table 135.  Descriptive statistics including mean, standard deviation, median, minimum and 
maximum values and change from baseline by study day will be summarized for each 
parameter in Table 136, Table 137, Table 138, Table 139, Table 140, Table 141.  Box plots 
illustrating the change from baseline for each laboratory parameter will be presented in 
Figure 58, Figure 59, Figure 60, Figure 61, Figure 62, and Figure 63. Subject visits with 
abnormal laboratory results, Grade 1 severity or higher, will be presented in Table 142 and 
Table 143 for Chemistry and Hematology parameters, respectively. 
A complete listing of individual clinical laboratory results will be presented in Listing 13 and 
Listing 14 for chemistry and hematology, respectively, sorted by subject ID, parameter, and 
visit number. 
9.7. 
Vital Signs and Physical Evaluations 
Vital signs oral temperature, systolic blood pressure, diastolic blood pressure, and pulse will 
be assessed prior to study vaccination on Day 1 and Day 22. The grading scale for vital sign 
evaluations is presented in Table 15. Summaries of vital signs by maximum severity will be 
tabulated by visit, and treatment group (Table 144, Table 145, Table 146, Table 147, 
Table 148). A listing of vital signs will be presented (Listing 15). 
Targeted physical examinations will be performed, if indicated, based a subject’s medical 
history. A listing of physical exam findings will be presented (Listing 16). 
9.8. 
Concomitant Medications 
Concomitant medications will be collected for the 30 days prior to the first study vaccination 
through 21 days after the second study vaccination. Concomitant medications will be coded 
to the Anatomical Therapeutic Classification using the WHO Drug Dictionary. The use of 
prior and concomitant medications taken during the study will be recorded on the CRFs. A 
by-subject listing of concomitant medication use will be presented (Listing 17). The use of 
concomitant medications during the study will be summarized by ATC1, ATC2 code, 
treatment group for the Safety population (Table 149). 
 


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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 Preliminary Report are indicated by *. 
 
 


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TABLE MOCK-UPS 
 
LIST OF TABLES 
Table 1: 
Study Design ................................................................................................................ 39 
Table 2: 
Schedule of Study Procedures – Group 1: Vaccination Period.................................... 40 
Table 3: 
Schedule of Study Procedures – Group 1: Follow-Up Period (Including early 
termination and unscheduled visits) ............................................................................. 43 
Table 4: 
Schedule of Study Procedures – Group 2: Vaccination Period.................................... 45 
Table 5: 
Schedule of Study Procedures – Group 2: Follow-Up Period (Including early 
termination and unscheduled visits) ............................................................................. 48 
Table 6: 
Schedule of Study Procedures – Group 3: Vaccination and Follow-up Periods .......... 50 
Table 7: 
Schedule of Study Procedures – Group 3: Early Termination and Unscheduled Visits
 ..................................................................................................................................... 52 
Table 8: 
Power (%) to Detect Safety Events .............................................................................. 53 
Table 9: 
Precisions of Binomial Confidence Intervals ............................................................... 53 
Table 10: 
Objective 1 -Minimum Detectable Difference in Proportion Responders with 80% 
Power (N = 50 per group) ............................................................................................ 53 
Table 11: 
Objective 2 - Minimum Detectable Difference in Proportion Responders with 80% 
Power ........................................................................................................................... 54 
Table 12: 
Distribution of Protocol Deviations by Category, Type and Treatment Group, All 
Enrolled Subjects ......................................................................................................... 55 
Table 13: 
Solicited Adverse Event Grading Scale – Local .......................................................... 57 
Table 14: 
Solicited Adverse Event Grading Scale - Systemic ..................................................... 58 
Table 15: 
Vital Signs Adverse Event Grading Scale ................................................................... 59 
Table 16: 
Laboratory Adverse Event Grading Scale ................................................................... 60 
Table 17: 
Ineligibility Summary of Screen Failures* .................................................................. 61 
Table 18: 
Analysis Populations by Treatment Group – All Enrolled Subjects* .......................... 62 
Table 19: 
Subject Disposition by Treatment Group, All Enrolled Subjects* .............................. 66 
Table 20: 
Dates of First Dose by Site and Treatment Group for the Safety Analysis Population 67 
Table 21: 
Dates of Second Dose by Site and Treatment Group for the Safety Analysis 
Population .................................................................................................................... 67 
Table 22: 
Dates of Third Dose by Site and Treatment Group for the Safety Analysis Population
 ..................................................................................................................................... 67 
Table 23: 
Summary of Categorical Demographic and Baseline Characteristics by Site, All 
Enrolled Subjects ......................................................................................................... 68 
Table 24: 
Summary of Continuous Demographic and Baseline Characteristics by Site, All 
Enrolled Subjects ......................................................................................................... 69 
Table 25: 
Summary of Categorical Demographic and Baseline Characteristics by Treatment 
Group, All Enrolled Subjects* ..................................................................................... 70 
Table 26: 
Summary of Continuous Baseline Characteristics by Treatment Group, All Enrolled 
Subjects* ...................................................................................................................... 71 
Table 27: 
Summary of Subjects with Prior or Concurrent Medical Conditions by MedDRA® 
System Organ Class and Treatment Group, Safety Analysis Population .................... 72 
Table 28: 
Summaries of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study 
Day and Treatment Group, Modified Intent-to-Treat Population* .............................. 73 
Table 29: 
Summaries of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study 
Day and Treatment Group, Per Protocol Population* ................................................. 74 


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Table 30: 
Summaries of Neutralizing Antibody Against 2017 A/H7N9 by Study Day and 
Treatment Group, Modified Intent-to-Treat Population* ............................................ 74 
Table 31: 
Summaries of Neutralizing Antibody Against 2017 A/H7N9 by Study Day and 
Treatment Group, Per Protocol Population* ................................................................ 74 
Table 32: 
Summaries of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains 
by Study Day and Treatment Group, Modified Intent-to-Treat Population* ............... 75 
Table 33: 
Summaries of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains 
by Study Day and Treatment Group, Per Protocol Population* .................................. 77 
Table 34: 
Summaries of Neutralizing Antibody Against Seasonal IIV4 Strains by Study Day and 
Treatment Group, Modified Intent-to-Treat Population* ............................................ 77 
Table 35: 
Summaries of Neutralizing Antibody Against Seasonal IIV4 Strains by Study Day and 
Treatment Group, Per Protocol Population* ................................................................ 77 
Table 36: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by 
Treatment Group and Age Group at 21 Days Post Second Dose of AS03 adjuvanted 
A/H7N9 Vaccine, Per-Protocol Population* ............................................................... 78 
Table 37: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by 
Treatment Group and Age Group at 180 Days Post Second Dose of AS03 adjuvanted 
A/H7N9 Vaccine, Per-Protocol Population ................................................................. 78 
Table 38: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Group and 
Age Group at 21 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per-
Protocol Population* .................................................................................................... 78 
Table 39: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Group and 
Age Group at 180 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per-
Protocol Population ...................................................................................................... 78 
Table 40: 
Summary of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains by 
Treatment Group and Age Group at 21 Days Post IIV4, Per-Protocol Population* ... 79 
Table 41: 
Summary of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains by 
Treatment Group and Age Group at 180 Days Post Second Dose of AS03 adjuvanted 
A/H7N9 Vaccine, Per-Protocol Population ................................................................. 80 
Table 42: 
Summary of Neutralizing Antibody Against Seasonal IIV4 Strains by Treatment 
Group and Age Group at 21 Days Post Second Dose of AS03 adjuvanted A/H7N9 
Vaccine, Per-Protocol Population* .............................................................................. 80 
Table 43: 
Summary of Neutralizing Antibody Against Seasonal IIV4 Strains by Treatment 
Group and Age Group at 180 Days Post Second Dose of AS03 adjuvanted A/H7N9 
Vaccine, Per-Protocol Population ................................................................................ 80 
Table 44: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by 
Treatment Group and Sex at 21 Days Post Second Dose of AS03 adjuvanted A/H7N9 
Vaccine, Per-Protocol Population* .............................................................................. 81 
Table 45: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by 
Treatment Group and Sex at 180 Days Post Second Dose of AS03 adjuvanted 
A/H7N9 Vaccine, Per-Protocol Population ................................................................. 81 
Table 46: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Group and 
Sex at 21 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per-Protocol 
Population* .................................................................................................................. 81 
Table 47: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Group and 
Sex at 180 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per-
Protocol Population ...................................................................................................... 81 
Table 48: 
Summary of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains by 
Treatment Group and Sex at 21 Days Post IIV4 Vaccination, Per-Protocol Population*
 ..................................................................................................................................... 82 


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Table 49: 
Summary of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains by 
Treatment Group and Sex at 180 Days Post IIV4 Vaccination, Per-Protocol Population
 ..................................................................................................................................... 83 
Table 50: 
Summary of Neutralizing Antibody Against Seasonal IIV4 Strains by Treatment 
Group and Sex at 21 Days Post IIV4 Vaccination, Per-Protocol Population* ............ 83 
Table 51: 
Summary of Neutralizing Antibody Against Seasonal IIV4 Strains by Treatment 
Group and Sex at 180 Days Post IIV4 Vaccination, Per-Protocol Population ............ 83 
Table 52: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by 
Treatment Group and BMI at 21 Days Post Second Dose of AS03 adjuvanted A/H7N9 
Vaccine, Per-Protocol Population* .............................................................................. 84 
Table 53: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by 
Treatment Group and BMI at 180 Days Post Second Dose of AS03 adjuvanted 
A/H7N9 Vaccine, Per-Protocol Population ................................................................. 84 
Table 54: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Group and 
BMI at 21 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per-
Protocol Population* .................................................................................................... 84 
Table 55: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Group and 
BMI at 180 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per-
Protocol Population ...................................................................................................... 84 
Table 56: 
Summary of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains by 
Treatment Group and BMI at 21 Days Post IIV4 Vaccination, Per-Protocol 
Population* .................................................................................................................. 85 
Table 57: 
Summary of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains by 
Treatment Group and BMI at 180 Days Post IIV4 Vaccination, Per-Protocol 
Population .................................................................................................................... 86 
Table 58: 
Summary of Neutralizing Antibody Against Seasonal IIV4 Strains by Treatment 
Group and BMI at 21 Days Post IIV4 Vaccination, Per-Protocol Population* ........... 86 
Table 59: 
Summary of Neutralizing Antibody Against Seasonal IIV4 Strains by Treatment 
Group and BMI at 180 Days Post IIV4 Vaccination, Per-Protocol Population ........... 86 
Table 60: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by 
Treatment Group and Prior Seasonal Influenza Vaccination at 21 Days Post Second 
Dose of AS03 adjuvanted A/H7N9 Vaccine, Per-Protocol Population* ..................... 87 
Table 61: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by 
Treatment Group and Prior Seasonal Influenza Vaccination at 180 Days Post Second 
Dose of AS03 adjuvanted A/H7N9 Vaccine, Per-Protocol Population ....................... 87 
Table 62: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Group and 
Prior Seasonal Influenza Vaccination at 21 Days Post Second Dose of AS03 
adjuvanted A/H7N9 Vaccine, Per-Protocol Population* ............................................. 87 
Table 63: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Group and 
Prior Seasonal Influenza Vaccination at 180 Days Post Second Dose of AS03 
adjuvanted A/H7N9 Vaccine, Per-Protocol Population ............................................... 87 
Table 64: 
Summary of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains by 
Treatment Group and Prior Seasonal Influenza Vaccination at 21 Days Post IIV4 
Vaccination, Per-Protocol Population* ........................................................................ 88 
Table 65: 
Summary of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains by 
Treatment Group and Prior Seasonal Influenza Vaccination at 180 Days Post IIV4 
Vaccination, Per-Protocol Population .......................................................................... 89 
Table 66: 
Summary of Neutralizing Antibody Against Seasonal IIV4 Strains by Treatment 
Group and Prior Seasonal Influenza Vaccination at 21 Days Post IIV4 Vaccination, 
Per-Protocol Population* ............................................................................................. 89 


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Table 67: 
Summary of Neutralizing Antibody Against Seasonal IIV4 Strains by Treatment 
Group and Prior Seasonal Influenza Vaccination at 180 Days Post IIV4 Vaccination, 
Per-Protocol Population ............................................................................................... 89 
Table 68: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule 
with HAI Seroconversion Against 2017 A/H7N9 at 21 Days post Second Dose of 
AS03 adjuvanted A/H7N9 Vaccine, Per Protocol Population* ................................... 90 
Table 69: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule 
with HAI Seroconversion Against 2017 A/H7N9 at 180 Days Post Second Dose of 
AS03 adjuvanted A/H7N9 Vaccine, Per Protocol Population * .................................. 90 
Table 70: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule 
with Neut Seroconversion Against 2017 A/H7N9 at 21 Days Post Second Dose of 
AS03 adjuvanted A/H7N9 Vaccine, Per Protocol Population ..................................... 90 
Table 71: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule 
with Neut Seroconversion Against 2017 A/H7N9 at 180 Days Post Second Dose of 
AS03 adjuvanted A/H7N9 Vaccine, Per Protocol Population ..................................... 90 
Table 72: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule 
with HAI Seroconversion Against Seasonal IIV4 Strains at 21 Days post IIV4 
Vaccination, Per Protocol Population* ........................................................................ 91 
Table 73: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule 
with HAI Seroconversion Against Seasonal IIV4 Strains at 180 Days Post IIV4 
Vaccination, Per Protocol Population .......................................................................... 91 
Table 74: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule 
with Neut Seroconversion Against Seasonal IIV4 Strains at 21 Days Post IIV4 
Vaccination, Per Protocol Population* ........................................................................ 91 
Table 75: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule 
with Neut Seroconversion Against Seasonal IIV4 Strains at 180 Days Post IIV4 
Vaccination, Per Protocol Population .......................................................................... 91 
Table 76: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule 
with HAI Seroconversion Against 2017 A/H7N9 at 21 Days Post Second Dose of 
AS03 adjuvanted A/H7N9 Vaccine, Adjusted for Baseline Covariates, Per Protocol 
Population* .................................................................................................................. 92 
Table 77: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule 
with HAI Seroconversion Against 2017 A/H7N9 at 180 Days Post Second Dose of 
AS03 adjuvanted A/H7N9 Vaccine, Adjusted for Baseline Covariates, Per Protocol 
Population .................................................................................................................... 93 
Table 78: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule 
with Neut Seroconversion Against 2017 A/H7N9 at 21 Days Post Second Dose of 
AS03 adjuvanted A/H7N9 Vaccine, Adjusted for Baseline Covariates, Per Protocol 
Population* .................................................................................................................. 93 
Table 79: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule 
with Neut Seroconversion Against 2017 A/H7N9 at 180 Days Post Second Dose of 
AS03 adjuvanted A/H7N9 Vaccine, Adjusted for Baseline Covariates, Per Protocol 
Population .................................................................................................................... 93 
Table 80: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule 
with HAI Seroconversion Against Seasonal IIV4 Strains at 21 Days Post IIV4 
Vaccination, Adjusted for Baseline Covariates, Per Protocol Population* ................. 94 
Table 81: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule 
with HAI Seroconversion Against Seasonal IIV4 Strains at 180 Days Post IIV4 
Vaccination, Adjusted for Baseline Covariates, Per Protocol Population ................... 95 


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Table 82: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule 
with Neut Seroconversion Against Seasonal IIV4 Strains at 21 Days Post IIV4 
Vaccination, Adjusted for Baseline Covariates, Per Protocol Population* ................. 95 
Table 83: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule 
with Neut Seroconversion Against Seasonal IIV4 Strains at 180 Days Post IIV4 
Vaccination, Adjusted for Baseline Covariates, Per Protocol Population ................... 95 
Table 84: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration 
Schedule with Log-Adjusted HAI Titer against 2017 A/H7N9 at 21 Days Post Second 
Dose of AS03 adjuvanted A/H7N9 Vaccine, Per Protocol Population* ..................... 96 
Table 85: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration 
Schedule with Log-Adjusted HAI Titer against 2017 A/H7N9 at 180 Days Post 
Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per Protocol Population ........... 96 
Table 86: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration 
Schedule with Log-Adjusted Neut Titer against 2017 A/H7N9 at 21 Days Post Second 
Dose of AS03 adjuvanted A/H7N9 Vaccine, Per Protocol Population* ..................... 96 
Table 87: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration 
Schedule with Log-Adjusted Neut Titer against 2017 A/H7N9 at 180 Days Post 
Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per Protocol Population ........... 96 
Table 88: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration 
Schedule with Log-Adjusted HAI Titer against Seasonal IIV4 Strains at 21 Days Post 
IIV4 Vaccination, Per Protocol Population*................................................................ 97 
Table 89: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration 
Schedule with Log-Adjusted HAI Titer against Seasonal IIV4 Strains at 180 Days 
Post IIV4 Vaccination, Per Protocol Population .......................................................... 97 
Table 90: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration 
Schedule with Log-Adjusted Neut Titer against Seasonal IIV4 Strains at 21 Days Post 
IIV4 Vaccination, Per Protocol Population*................................................................ 97 
Table 91: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration 
Schedule with Log-Adjusted Neut Titer against Seasonal IIV4 Strains at 180 Days 
Post IIV4 Vaccination, Per Protocol Population .......................................................... 97 
Table 92: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration 
Schedule with Log-Adjusted HAI Titer against 2017 A/H7N9 at 21 Days Post Second 
Dose of AS03 adjuvanted A/H7N9 Vaccine, Adjusted for Baseline Covariates, Per 
Protocol Population* .................................................................................................... 98 
Table 93: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration 
Schedule with Log-Adjusted HAI Titer at 180 Days Post Second Dose of AS03 
adjuvanted A/H7N9 Vaccine, Adjusted for Baseline Covariates, Per Protocol 
Population .................................................................................................................... 98 
Table 94: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration 
Schedule with Log-Adjusted Neut Titer at 21 Days Post Second Dose of AS03 
adjuvanted A/H7N9 Vaccine, Adjusted for Baseline Covariates, Per Protocol 
Population* .................................................................................................................. 98 
Table 95: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration 
Schedule with Log-Adjusted Neut Titer at 180 Days Post Second Dose of AS03 
adjuvanted A/H7N9 Vaccine, Adjusted for Baseline Covariates, Per Protocol 
Population .................................................................................................................... 98 
Table 96: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration 
Schedule with Log-Adjusted HAI Titer against Seasonal IIV4 Strains at 21 Days Post 
IIV4 Vaccination, Adjusted for Baseline Covariates, Per Protocol Population* ......... 99 


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Table 97: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration 
Schedule with Log-Adjusted HAI Titer against Seasonal IIV4 Strains at 180 Days 
Post IIV4 Vaccination, Adjusted for Baseline Covariates, Per Protocol Population . 100 
Table 98: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration 
Schedule with Log-Adjusted Neut Titer against Seasonal IIV4 Strains at 21 Days Post 
IIV4 Vaccination, Adjusted for Baseline Covariates, Per Protocol Population ......... 100 
Table 99: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration 
Schedule with Log-Adjusted Neut Titer against Seasonal IIV4 Strains at 180 Days 
Post IIV4 Vaccination, Adjusted for Baseline Covariates, Per Protocol Population . 100 
Table 100: 
Overall Summary of Adverse Events, Safety Population* ........................................ 101 
Table 101: 
Number of Adverse Events Occurring in 5% of Subjects in Any Treatment Group by 
MedDRA® System Organ Class and Preferred Term, and Treatment Group - Safety 
Population .................................................................................................................. 103 
Table 102: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% 
Confidence Intervals by Symptom and Treatment Group (Safety Population) – Post 
Any Study Dose* ....................................................................................................... 104 
Table 103: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% 
Confidence Intervals by Symptom and Treatment Group (Safety Population) – Post 
Study Dose 1* ............................................................................................................ 105 
Table 104: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% 
Confidence Intervals by Symptom and Treatment Group (Safety Population) – Post 
Study Dose 2* ............................................................................................................ 105 
Table 105: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% 
Confidence Intervals by Symptom and Treatment Group (Safety Population) – Post 
Study Dose 3* ............................................................................................................ 105 
Table 106: 
Logistic Regression Model to Evaluate the Relationship of Treatment with Reporting 
Any Local Event Post Any Study Dose (Safety Population) * .................................. 106 
Table 107: 
Logistic Regression Model to Evaluate the Relationship of Treatment with Reporting 
Any Systemic Event Post Any Study Dose (Safety Population) * ............................ 106 
Table 108: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Maximum Severity and Treatment Group (Safety Population) – Post Any Study Dose*
 ................................................................................................................................... 107 
Table 109: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Maximum Severity and Treatment Group (Safety Population) – Post Study Dose 1*
 ................................................................................................................................... 111 
Table 110: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Maximum Severity and Treatment Group (Safety Population) – Post Study Dose 2*
 ................................................................................................................................... 111 
Table 111: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Maximum Severity and Treatment Group (Safety Population) – Post Study Dose 3*
 ................................................................................................................................... 111 
Table 112: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Severity, Day Post Dose, and Treatment Group (Safety Population) – Post Any Study 
Dose ........................................................................................................................... 112 
Table 113: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Severity, Day Post Dose, and Treatment Group (Safety Population) – Post Study Dose 
1 ................................................................................................................................. 115 
Table 114: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Severity, Day Post Dose, and Treatment Group (Safety Population) – Post Study Dose 
2 ................................................................................................................................. 115 


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Table 115: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Severity, Day Post Dose, and Treatment Group (Safety Population) – Post Study Dose 
3 ................................................................................................................................. 115 
Table 116: 
Comparison of the Number and Percentage of Subjects Experiencing Solicited 
Systemic Events by Dose and Treatment Group – Safety Population ....................... 116 
Table 117: 
Comparison of the Number and Percentage of Subjects Experiencing Solicited Local 
Events by Dose and Treatment Group  – Safety Population ...................................... 117 
Table 118: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events with 
95% Confidence Intervals by MedDRA® System Organ Class and Preferred Term, 
and Treatment Group – Safety Population* ............................................................... 118 
Table 119: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events by 
MedDRA® System Organ Class and Preferred Term, Maximum Severity, 
Relationship, and Treatment Group – Safety Population* ........................................ 119 
Table 120: 
Number and Percentage of Subjects Experiencing Non-Serious Related Unsolicited 
Adverse Events by MedDRA® System Organ Class and Preferred Term, Maximum 
Severity, and Treatment Group – Safety Population ................................................. 121 
Table 121: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events Within 
21 Days Post Dose by MedDRA® System Organ Class and Preferred Term, Day Post 
Dose, and Treatment Group – Safety Population ...................................................... 123 
Table 122: 
Number and Percentage of Subjects Experiencing Non-Serious, Related Unsolicited 
Adverse Events Within 21 Days Post Dose by MedDRA® System Organ Class and 
Preferred Term, Dose and Treatment Group – Safety Population ............................. 125 
Table 123: 
Number of Unsolicited Adverse Events by MedDRA® System Organ Class and 
Preferred Term, Day Post Dose, and Treatment Group – Safety Population............. 127 
Table 124: 
Listing of Serious Adverse Events * .......................................................................... 129 
Table 125: 
Listing of Medically Attended Adverse Events* ....................................................... 130 
Table 126: 
Listing of Potentially Immune Mediated Medical Conditions* ................................. 130 
Table 127: 
Listing of New Onset Chronic Medical Conditions* ................................................. 130 
Table 128: 
Listing of Non-Serious, Unsolicited, Moderate or Severe Adverse Events* ............. 130 
Table 129: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Treatment 
Group (Safety Population)  – All Laboratory Parameters * ....................................... 132 
Table 130: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Treatment 
Group (Safety Population)  – White Blood Cells* .................................................... 134 
Table 131: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Treatment 
Group (Safety Population)  – Hemoglobin* .............................................................. 135 
Table 132: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Treatment 
Group (Safety Population)  – Platelets* ..................................................................... 135 
Table 133: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Treatment 
Group (Safety Population)  – Alanine aminotransferase (ALT) * ............................. 135 
Table 134: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Treatment 
Group (Safety Population)  – Total Bilirubin * ......................................................... 135 
Table 135: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Treatment 
Group (Safety Population)  – Creatinine* .................................................................. 135 
Table 136: 
Laboratory Summary Statistics of Value and Change from Baseline by Study Day, and 
Treatment Group (Safety Population)  – White Blood Cells* ................................... 136 
Table 137: 
Laboratory Summary Statistics of Value and Change from Baseline by Study Day, and 
Treatment Group (Safety Population)  – Hemoglobin* ............................................. 137 
Table 138: 
Laboratory Summary Statistics of Value and Change from Baseline by Study Day, and 
Treatment Group (Safety Population)  – Platelets* ................................................... 137 
Table 139: 
Laboratory Summary Statistics of Value and Change from Baseline by Study Day, and 
Treatment Group (Safety Population)  – Alanine Aminotransferase* (ALT) ........... 137 


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Table 140: 
Laboratory Summary Statistics of Value and Change from Baseline by Study Day, and 
Treatment Group (Safety Population)  – Total Bilirubin* ......................................... 137 
Table 141: 
Laboratory Summary Statistics of Value and Change from Baseline by Study Day, and 
Treatment Group (Safety Population)  – Creatinine* ................................................ 137 
Table 142: 
Listing of Abnormal Laboratory Results - Chemistry ............................................... 139 
Table 143: 
Listing of Abnormal Laboratory Results - Hematology ............................................ 140 
Table 144: 
Vital Signs by Assessment, Maximum Severity, Study Day, Treatment Group (Safety 
Population)  – Any Assessment* ............................................................................... 141 
Table 145: 
Vital Signs by Assessment, Maximum Severity, Study Day, Treatment Group (Safety 
Population)  – Oral Temperature ............................................................................... 141 
Table 146: 
Vital Signs by Assessment, Maximum Severity, Study Day, and Treatment Group 
(Safety Population)  – Systolic Blood Pressure ......................................................... 142 
Table 147: 
Vital Signs by Assessment, Maximum Severity, Study Day, and Treatment Group 
(Safety Population)  – Diastolic Blood Pressure ........................................................ 143 
Table 148: 
Vital Signs by Assessment, Maximum Severity, Study Day, and Treatment Group 
(Safety Population)  – Pulse ....................................................................................... 143 
Table 149: 
Number and Percentage of Subjects with Prior and Concurrent Medications by WHO 
Drug Classification and Treatment Group – Safety Population................................. 144 
 
 


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9.1  
Overall Study Design and Plan Description 
Table 1: 
Study Design 
 
Day 1 
Dose 1 
Approximately Day 22 
Dose 2 
Approximately Day 43 
Dose 3 
Group 1 
(Age 19-64) 
 n=60 
Dose 1 (First and Second 
Study Vaccinations):  
Sanofi Pasteur H7N9 
vaccine 3.75 mcg/ PBS 
diluent, plus GSK AS03 
adjuvant 
+ IIV4 
Dose 2 (Third Study 
Vaccination): 
Sanofi Pasteur H7N9 
vaccine 3.75 mcg/ PBS 
diluent, plus GSK AS03 
adjuvant 
 
N/A  
Group 2 
(Age 19-64) 
 n=60 
Dose 1 (First Study 
Vaccination): 
IIV4 
 
Dose 2 (Second Study 
Vaccination): 
Sanofi Pasteur H7N9 
vaccine 3.75 mcg/ PBS 
diluent, plus GSK AS03 
adjuvant 
 
Dose 3 (Third Study 
Vaccination): 
Sanofi Pasteur H7N9 
vaccine 3.75 mcg/ PBS 
diluent, plus GSK AS03 
adjuvant 
 
Group 3 
(Age 19-64) 
 n=30 
Dose 1 (First Study 
Vaccination): 
IIV4  
 
N/A 
N/A 
Total 
Enrollment, 
n = ~150 
Blood for HAI/Neut assays for 2017 H7N9 IIV will be collected:  
• 
for Group 1 on Days 1 (baseline), 22, and 43, and at approximately 180 
days post second adjuvanted 2017 H7N9 IIV dose (Day 202) 
• 
for Group 2, on Days 22 (baseline), 43, and 64, and at approximately  
180 days post second 2017 H7N9 IIV dose (Day 223). 
Serological antibody assays will also be performed against the vaccine viruses in 
IIV4 from serum samples collected at baseline (Day 1) and approximately 21 and 
180 days following receipt of IIV4 (Groups 1, 2 and 3). 
Safety Lab Timepoints: 
Group 1: 4 timepoints per subject (Days 1, 8, 22, and 29)  
Group 2: 6 timepoints per subject (Days 1, 8, 22, 29, 43, and 50) 
Group 3: 2 timepoints per subject (Days 1 and 8) and Early Termination and /or 
Unscheduled Visits 
 
 


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9.5.1 Efficacy/Immunogenicity and Safety Measurements Assessed and Flow Chart 
Table 2: 
Schedule of Study Procedures – Group 1: Vaccination Period 
Study Visit 
Number 
V00 
V01 
V02 
V03 
V04ψ 
V05 
V06 
Study Day post 
Dose 1 
Screening 
(Optional) 
D -28 to -1 
Enrollment 
Dose 1 
D1 
D4[±1] 
D8[+2] 
D22[+7] 
D25 
D29 
Study Day post 
Dose 2 
 
 
 
 
Dose 2 
D1 
D4[±1] 
D8[+2] 
Obtain Informed 
Consent∞ 
X 
X¬ 
 
 
 
 
 
Collect 
Demographic 
Information 
X 
X†* 
 
 
 
 
 
Review Eligibility 
Criteria 
X 
X†¬1 
 
 
X† 
 
 
Medical History@ 
X 
X†¬* 
 
X 
X 
 
X 
Concomitant 
Medications 
Xς 
X†¬ς 
Xς 
Xς 
Xς 
Xς 
Xς 
Vital Signs$ 
(Oral 
Temperature%, 
Pulse, and BP) 
X 
X† 
 
 
X†2 
 
 
Height and Weight 
X 
X†* 
 
 
 
 
 
Physical 
Examination3 
X 
{X}†* 
 
{X} 
{X} 
 
{X} 
Urine or Serum 
Pregnancy Test 
X^ 
X†^ 
 
 
X†^ 
 
 
Venous Blood 
Collection for ESR 
X 
X≠* 
 
 
 
 
 
Venous Blood 
Collection for 
Clinical Safety 
Laboratory 
Evaluations~ 
 
X† 
 
X 
X† 
 
X 
Venous Blood 
Collection for 
Immunogenicity 
Assays 
 
X† 
 
 
X† 
 
 
Serum Sample 
Collected for Future 
Research4 
 
X† 
 
X 
X† 
 
X 
Safety Follow-up 
Phone Call 
 
 
X 
 
 
X 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
 
14 November 2018 
Table 2: 
Schedule of Study Procedures – Group 1: Vaccination Period (continued) 
- 41 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Study Visit 
Number 
V00 
V01 
V02 
V03 
V04ψ 
V05 
V06 
Study Day post 
Dose 1 
Screening 
(Optional) 
D -28 to -1 
Enrollment 
Dose 1 
D1 
D4[±1] 
D8[+2] 
D22[+7] 
D25 
D29 
Study Day post 
Dose 2 
 
 
 
 
Dose 2 
D1 
D4[±1] 
D8[+2] 
Enrollment in 
AdvantageEDCSM 
and Randomization 
 
X† 
 
 
 
 
 
Pre-Administration 
Reactogenicity 
Assessments 
 
X† 
 
 
X 
 
 
 Vaccination 
 
X 
 
 
X 
 
 
20-minute 
Evaluation After 
Study Vaccination 
 
X 
 
 
X 
 
 
Examine Study 
Vaccination Site 
 
X 
 
X 
X 
 
X 
Post-Administration 
Reactogenicity 
Assessments 
 
X 
 
 
X 
 
 
Distribute Memory 
Aid and Study-
Related Materials 
 
X 
 
 
X 
 
 
Review Memory 
Aid 
 
 
X 
X 
 
X 
X 
AE/SAE 
Assessment  
 
X& 
X& 
X& 
X& 
X& 
X& 
∞ Prior to study procedures. 
† Prior to study vaccination.  
1 Review results of clinical screening (ESR) or safety laboratory evaluations. 
¬ Review/confirm information or activity in subjects previously consented and screened. 
@ Complete medical history will be obtained by interview of subjects at screening (optional) or on Day 1 prior to the 
first study vaccination and interim medical history will be obtained by interview of subjects at follow-up visits after 
Dose 1 
ς  Receipt of non-study influenza vaccines will be solicited through approximately 180 days after the last study 
vaccination, and reported in the eCRF. 
* Not required if done at the optional screening visit. 
√ All current medications and medications taken within 60 days prior to signing the ICF. 
$ Vital signs assessed on Day 1 prior to the first study vaccination will be considered as baseline. 
% Subjects must not eat or drink anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
2 Vital signs are not required for subjects who are discontinued from receipt of the third study vaccination and are being 
followed for safety. 
3 At the screening (or baseline if not done at screening) visit, a physical examination will be performed on all subjects 
to include the following organs and organ systems: skin, head and neck, lungs, heart, liver, spleen, extremities, lymph 
nodes, and nervous system. 
{} Targeted physical examination if indicated based on review of interim medical history. 
^ May be performed on all women of childbearing potential at screening (optional) and will be performed within 24 
hours prior to each vaccination and results must be negative and known prior to each study vaccination. 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
 
14 November 2018 
Table 2: 
Schedule of Study Procedures – Group 1: Vaccination Period (continued) 
- 42 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Study Visit 
Number 
V00 
V01 
V02 
V03 
V04ψ 
V05 
V06 
Study Day post 
Dose 1 
Screening 
(Optional) 
D -28 to -1 
Enrollment 
Dose 1 
D1 
D4[±1] 
D8[+2] 
D22[+7] 
D25 
D29 
Study Day post 
Dose 2 
 
 
 
 
Dose 2 
D1 
D4[±1] 
D8[+2] 
≠ To be performed locally by the site. The ESR value must be confirmed as <30 mm/hr prior to randomization and first 
study vaccination. 
~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr. 
Ψ  Subjects who do not receive the third study vaccination will continue with follow-up safety assessments (may be 
conducted by phone call) rather than in person continuing through approximately 12 months after their first study 
vaccination. These subjects will also be encouraged to provide a venous blood sample for immunogenicity assays at 
approximately 21 and 180 days after their first study vaccination. 
4 For subjects who have consented to collected of serum for future research. 
& Inclusive of reactogenicity assessments performed on the day of each vaccination through 7 days after each study 
vaccination.  


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 43 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 3: 
Schedule of Study Procedures – Group 1: Follow-Up Period (Including early termination and unscheduled visits) 
Study Visit Number 
     
V07 
 
V08 
V09ψ 
V10 
V11 
Early 
Termination 
(if needed) 
Unscheduled 
(if needed) 
Study Day post Dose 1 
D43 
D64 
D181 
[±14] 
 D202 
 D387 
 
 
Study Day post Dose 2 
D22[+7] 
D43[+7] 
 
 D181[±14] 
     
D366[±14] 
 
 
Medical History@ 
X 
X 
X 
X 
 
X 
X (if indicated) 
Concomitant 
Medications 
Xς 
Xς 
Xς 
Xς 
 
X (if within 21 days after last 
study vaccination and receipt 
of any non-study influenza 
vaccine will be recorded if 
within 180 days after the 2nd 
study vaccination) 
X (if within 21 days after 
last study vaccination and 
receipt of any non-study 
influenza vaccine will be 
recorded if within 180 
days after the 2nd study 
vaccination) 
Vital Signs$ 
(Oral Temperature%, 
Pulse, and BP) 
 
 
 
 
 
X (may be obtained if 
indicated) 
X (may be obtained if 
indicated) 
Physical Examination3 
{X} 
{X} 
{X} 
{X} 
 
{X} 
{X} 
Venous Blood 
Collection for Clinical 
Safety Laboratory 
Evaluations~ 
 
 
 
 
 
X (if within 7 days after the 
last study vaccination) 
X (if indicated) 
Venous Blood 
Collection for  
Immunogenicity  Assays 
X 
 
X 
X 
 
X(if within 21 days after last 
study vaccination 
X(if within 21 days after 
last study vaccination 
Serum Sample Collected 
for Future Research4 
X 
X 
X 
X 
 
X(if within 21 days after last  
study vaccination 
X(if within 21 days after 
last  study vaccination   


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
Table 3: 
Schedule of Study Procedures – Group 1: Follow-Up Period (Including early termination and unscheduled visits) (continued) 
- 44 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Study Visit Number 
     
V07 
 
V08 
V09ψ 
V10 
V11 
Early 
Termination 
(if needed) 
Unscheduled 
(if needed) 
Study Day post Dose 1 
D43 
D64 
D181 
[±14] 
 D202 
 D387 
 
 
Study Day post Dose 2 
D22[+7] 
D43[+7] 
 
 D181[±14] 
     
D366[±14] 
 
 
Safety Follow-up Phone 
Call 
 
 
 
 
 
X 
 
 
Examine Study 
Vaccination Site 
 
 
 
 
 
X (if within 7 days after last 
study vaccination) 
X (if within 7 days after 
last study vaccination) 
Post-Administration 
Reactogenicity 
Assessments 
 
 
 
 
 
X (if within 7 days after last 
study vaccination) 
X (if within 7 days after 
last study vaccination) 
Review Memory Aid 
 
 
 
 
 
X (if within 7 days after last 
study vaccination) 
X (if within 7 days after 
last study vaccination) 
AE/SAE Assessment 
X 
X 
X 
X 
X 
X& 
X& 
@ Complete medical history will be obtained by interview of subjects at screening (optional) or on Day 1 prior to the first study vaccination and interim medical history will be 
obtained by interview of subjects at follow-up visits after Dose 1 
ς  Receipt of non-study influenza vaccines will be solicited through approximately 180 days after the last study vaccination, and reported in the eCRF. 
$ Vital signs assessed on Day 1 prior to the first study vaccination will be considered as baseline. 
% Subjects must not eat or drink anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
{} Targeted physical examination if indicated based on review of interim medical history 
.~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr. 
Ψ  Subjects who do not receive the third study vaccination will continue with follow-up safety assessments (may be conducted by phone call) rather than in person continuing through 
approximately 12 months after their first study vaccination. These subjects will also be encouraged to provide a venous blood sample for immunogenicity assays at approximately 
21 and 180 days after their first study vaccination. 
4 For subjects who have consented to collected of serum for future use. 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 45 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 4: 
Schedule of Study Procedures – Group 2: Vaccination Period 
Study Visit Number 
V00 
V01 
V02 
V03 
V04ψ 
V05 
V06 
V07ψ 
V08 
Study Day post Dose 1 
Screening 
(Optional) 
D -28 to -1 
Enrollment  
Dose 1 
D1 
D4[±1] 
D8[+2] 
D22[+7] 
D25  
D29 
D43 
D46 
Study Day post Dose 2 
 
 
 
 
Dose 2 
D1 
D4[±1] 
D8[+2] 
D22[+7] 
D25 
Study Day post Dose 3 
 
 
 
 
 
 
 
Dose 3 
D1 
D4[±1] 
Study Procedure/Evaluation 
 
Obtain Informed 
Consent∞ 
X 
X¬ 
 
 
 
 
 
 
 
Collect Demographic 
Information 
X 
X†* 
 
 
 
 
 
 
 
Review Eligibility 
Criteria 
X 
X†¬1 
 
 
X† 
 
 
X† 
 
Medical History@ 
X 
X†¬* 
 
X 
X 
 
X 
X 
 
Concomitant Medications 
Xς 
X†¬ς 
Xς 
Xς 
Xς 
Xς 
Xς 
Xς 
Xς 
Vital Signs$ 
(Oral Temperature%, 
Pulse, and BP) 
X 
X† 
 
 
X†2 
 
 
X†2 
 
Height and Weight 
X 
X†* 
 
 
 
 
 
 
 
Physical Examination3 
X 
X†* 
 
{X} 
{X} 
 
{X} 
{X} 
 
Urine or Serum 
Pregnancy Test 
X^ 
X†^ 
 
 
X†^ 
 
 
X†^ 
 
Venous Blood Collection 
for ESR 
X 
X≠* 
 
 
 
 
 
 
 
Venous Blood Collection 
for Clinical Safety 
Laboratory Evaluations~ 
 
X† 
 
X 
X† 
 
X 
X† 
 
Venous Blood Collection 
for Immunogenicity 
Assays 
 
X† 
 
 
X† 
 
 
X† 
 
Serum Sample Collected 
for Future Research4 
 
X† 
 
X 
X† 
 
X 
X† 
 
Safety Follow-up Phone 
Call 
 
 
X 
 
 
X 
 
 
X 
Enrollment in 
AdvantageEDCSM and 
Randomization 
 
X† 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
Table 4: 
Schedule of Study Procedures – Group 2: Vaccination Period (continued) 
- 46 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Study Visit Number 
V00 
V01 
V02 
V03 
V04ψ 
V05 
V06 
V07ψ 
V08 
Study Day post Dose 1 
Screening 
(Optional) 
D -28 to -1 
Enrollment  
Dose 1 
D1 
D4[±1] 
D8[+2] 
D22[+7] 
D25  
D29 
D43 
D46 
Study Day post Dose 2 
 
 
 
 
Dose 2 
D1 
D4[±1] 
D8[+2] 
D22[+7] 
D25 
Study Day post Dose 3 
 
 
 
 
 
 
 
Dose 3 
D1 
D4[±1] 
Study Procedure/Evaluation 
 
Pre-Administration 
Reactogenicity 
Assessments 
 
X† 
 
 
X 
 
 
X 
 
Vaccination 
 
X 
 
 
X 
 
 
X 
 
20-minute Evaluation 
After Vaccination 
 
X 
 
 
X 
 
 
X 
 
Examine Vaccination Site 
 
X 
 
X 
X 
 
X 
X 
 
Post-Administration 
Reactogenicity 
Assessments 
 
X 
 
 
X 
 
 
X 
 
Distribute Memory Aid 
and Study-Related 
Materials 
 
X 
 
 
X 
 
 
X 
 
Review Memory Aid 
 
 
X 
X 
 
X 
X 
 
X 
AE/SAE Assessment  
 
X& 
X& 
X& 
X& 
X& 
X& 
X& 
X& 
∞ Prior to study procedures. 
† Prior to study vaccination.  
1 Review results of clinical screening (ESR) or safety laboratory evaluations. 
¬ Review/confirm information or activity in subjects previously consented and screened. 
@ Complete medical history will be obtained by interview of subjects at screening (optional) or on Day 1 prior to the 
first study vaccination and interim medical history will be obtained by interview of subjects at follow-up visits after 
the first study vaccination. 
ς  Receipt of non-study influenza vaccines will be solicited through approximately 180 days after the last study 
vaccination, and reported in the eCRF. 
* Not required if done at the optional screening visit. 
√ All current medications and medications taken within 60 days prior to signing the ICF. 
$ Vital signs assessed on Day 1 prior to the first study vaccination will be considered as baseline. 
% Subjects must not eat or drink anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
2 Vital signs are not required for subjects who are discontinued from receipt of the third study vaccination and are being 
followed for safety. 
3 At the screening (or baseline if not done at screening) visit, a physical examination will be performed on all subjects 
to include the following organs and organ systems: skin, head and neck, lungs, heart, liver, spleen, extremities, lymph 
nodes, and nervous system. 
{} Targeted physical examination if indicated based on review of interim medical history. 
^ May be performed on all women of childbearing potential at screening (optional) and will be performed within 24 
hours prior to each vaccination and results must be negative and known prior to each study vaccination. 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
Table 4: 
Schedule of Study Procedures – Group 2: Vaccination Period (continued) 
- 47 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Study Visit Number 
V00 
V01 
V02 
V03 
V04ψ 
V05 
V06 
V07ψ 
V08 
Study Day post Dose 1 
Screening 
(Optional) 
D -28 to -1 
Enrollment  
Dose 1 
D1 
D4[±1] 
D8[+2] 
D22[+7] 
D25  
D29 
D43 
D46 
Study Day post Dose 2 
 
 
 
 
Dose 2 
D1 
D4[±1] 
D8[+2] 
D22[+7] 
D25 
Study Day post Dose 3 
 
 
 
 
 
 
 
Dose 3 
D1 
D4[±1] 
Study Procedure/Evaluation 
 
≠ To be performed locally by the site. The ESR value must be confirmed as <30 mm/hr prior to randomization and first 
study vaccination. 
~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr. 
Ψ  Subjects who do not receive the third study vaccination will continue with follow-up safety assessments (may be 
conducted by phone call) rather than in person continuing through approximately 12 months after their first study 
vaccination. These subjects will also be encouraged to provide a venous blood sample for immunogenicity assays at 
approximately 21 and 180 days after their first study vaccination. 
4 For subjects who have consented to collected of serum for future use. 
& Inclusive of reactogenicity assessments performed on the day of each vaccination through 7 days after each study 
vaccination.  


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 48 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 5: 
Schedule of Study Procedures – Group 2: Follow-Up Period (Including early 
termination and unscheduled visits) 
Study Visit 
Number 
V09 
V10 
V11ψ 
V12 
V13 
Early 
Terminati
on (if 
needed) 
Unschedu
led (if 
needed) 
Study Day post 
Dose 1 
D50 
D64 
D181 [±14] 
D223 
D408 
 
 
Study Day post 
Dose 2 
D29 
D43 
 
D202 
D387 
 
 
Study Day post 
Dose 3 
 D8[+2] 
 D22[+7] 
 
D181[±14] 
D366[±14] 
 
 
Medical 
History@ 
X 
X 
X 
X 
 
X 
X (if indicated) 
Concomitant 
Medications 
Xς 
Xς 
Xς 
Xς 
 
X (if within 21 days after last 
study vaccination and receipt 
of any non-study influenza 
vaccine will be recorded if 
within 180 days after the 2nd 
study vaccination) 
X (if within 21 days after last 
study vaccination and receipt 
of any non-study influenza 
vaccine will be recorded if 
within 180 days after the 2nd 
study vaccination) 
Vital Signs$ 
(Oral 
Temperature%, 
Pulse, and BP) 
 
 
 
 
 
X (may be obtained if 
indicated) 
X (may be obtained if 
indicated) 
Physical 
Examination3 
{X} 
{X} 
{X} 
{X} 
 
{X} 
{X} 
Venous Blood 
Collection for 
Clinical Safety 
Laboratory 
Evaluations~ 
X 
 
 
 
 
X (if within 7 days after the 
last study vaccination) 
X (if indicated) 
Venous Blood 
Collection for  
Immunogenicity  
Assays 
 
X 
X 
X 
 
X(if within 21 days after last 
study vaccination 
X(if within 21 days after last 
study vaccination 
Serum Sample 
Collected for 
Future 
Research4 
X 
X 
X 
X 
 
X(if within 21 days after last  
study vaccination 
X(if within 21 days after last  
study vaccination 
Safety Follow-
up Phone Call 
 
 
 
 
X 
 
 
Examine 
Vaccination 
Site 
X 
 
 
 
 
X (if within 7 days after last 
study vaccination) 
X (if within 7 days after last 
study vaccination) 
Post-
Administration 
Reactogenicity 
Assessments 
 
 
 
 
 
X (if within 7 days after last 
study vaccination) 
X (if within 7 days after last 
study vaccination) 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
Table 5: 
Schedule of Study Procedures – Group 2: Follow-Up Period (Including early 
termination and unscheduled visits) (continued) 
- 49 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Study Visit 
Number 
V09 
V10 
V11ψ 
V12 
V13 
Early 
Terminati
on (if 
needed) 
Unschedu
led (if 
needed) 
Study Day post 
Dose 1 
D50 
D64 
D181 [±14] 
D223 
D408 
 
 
Study Day post 
Dose 2 
D29 
D43 
 
D202 
D387 
 
 
Study Day post 
Dose 3 
 D8[+2] 
 D22[+7] 
 
D181[±14] 
D366[±14] 
 
 
Review 
Memory Aid 
X 
 
 
 
 
X (if within 7 days after last 
study vaccination) 
X (if within 7 days after last 
study vaccination) 
AE/SAE 
Assessment 
X& 
X 
X 
X 
X 
X& 
X& 
@ Complete medical history will be obtained by interview of subjects at screening (optional) or on Day 1 prior to the 
first study vaccination and interim medical history will be obtained by interview of subjects at follow-up visits after 
the first study vaccination. 
ς  Receipt of non-study influenza vaccines will be solicited through approximately 180 days after the last study 
vaccination, and reported in the eCRF. 
$ Vital signs assessed on Day 1 prior to the first study vaccination will be considered as baseline. 
% Subjects must not eat or drink anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
{} Targeted physical examination if indicated based on review of interim medical history. 
~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr. 
Ψ  Subjects who do not receive the second or third study vaccination will continue with follow-up safety assessments 
(may be conducted by phone call) rather than in person continuing through approximately 12 months after their first 
study vaccination. These subjects will also be encouraged to provide a venous blood sample for immunogenicity 
assays at approximately 21 and 180 days after their first study vaccination. 
4 For subjects who have consented to collected of serum for future use 
& Inclusive of reactogenicity assessments performed on the day of each study vaccination through 7 days after each 
study vaccination.  
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 50 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 6: 
Schedule of Study Procedures – Group 3: Vaccination and Follow-up Periods 
Study Visit Number 
V00 
V01 
V02 
V03 
 
V04ψ 
 
V05 
 
V06 
 
V07ψ 
 
V08 
Study Day post  
 dose 
Screening 
(Optional) 
D -28 to -1 
Enrollment 
Dose 1 
D1 
D4[±1] 
D8[+2] 
 
D22[+7] 
 
D43[+7] 
 
D64[+7] 
 
D181[±14] 
 
D366[±14] 
Obtain Informed 
Consent 
X 
X¬ 
 
 
 
 
 
 
 
Collect Demographic 
Information 
X 
X†* 
 
 
 
 
 
 
 
Review Eligibility 
Criteria 
X 
X†¬1 
 
 
 
 
 
 
 
Medical History@ 
X 
X†¬* 
 
X 
X 
X 
X 
X 
 
Concomitant 
Medications 
Xς 
X†¬ς 
Xς 
Xς 
Xς 
 
Xς 
Xς 
 
Xς 
 
 
 
Vital Signs$ 
(Oral Temperature%, 
Pulse, and BP) 
X 
X† 
 
 
 
 
 
 
 
Height and Weight 
X 
X†* 
 
 
 
 
 
 
 
Physical Examination3 
X 
{X}†* 
 
{X} 
{X} 
{X} 
{X} 
{X} 
 
Urine or Serum 
Pregnancy Test 
X^ 
X†^ 
 
 
 
 
 
 
 
Venous Blood 
Collection for ESR 
X 
X≠* 
 
 
 
 
 
 
 
Venous Blood 
Collection for Clinical 
Safety Laboratory 
Evaluations~ 
 
X 
 
X 
 
 
 
 
 
 
 
Venous Blood 
Collection for 
Immunogenicity 
Assays 
 
X† 
 
 
 
X 
 
 
 
 
 
X 
 
Serum Sample 
Collected for Future 
Research4 
 
X† 
 
X 
X 
X 
X 
X 
 
Safety Follow-up 
Phone Call 
 
 
X 
 
 
 
 
 
X 
Enrollment in 
AdvantageEDCSM and 
Randomization 
 
X† 
 
 
 
 
 
 
 
Pre-Administration 
Reactogenicity 
Assessments 
 
X† 
 
 
 
 
 
 
 
Vaccination 
 
X 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
Table 6: 
Schedule of Study Procedures – Group 3: Vaccination and Follow-up Periods 
(continued) 
- 51 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Study Visit Number 
V00 
V01 
V02 
V03 
 
V04ψ 
 
V05 
 
V06 
 
V07ψ 
 
V08 
Study Day post  
 dose 
Screening 
(Optional) 
D -28 to -1 
Enrollment  
Dose 1 
D1 
D4[±1] 
D8[+2] 
 
D22[+7] 
 
D43[+7] 
 
D64[+7] 
 
D181[±14] 
 
D366[±14] 
20-minute Evaluation 
After Vaccination 
 
X 
 
 
 
 
 
 
 
Examine Vaccination 
Site 
 
X 
 
X 
 
 
 
 
 
Post-Administration 
Reactogenicity 
Assessments 
 
X 
 
 
 
 
 
 
 
Distribute Memory 
Aid and Study-Related 
Materials 
 
X 
 
 
 
 
 
 
 
Review Memory Aid 
 
 
X 
X 
 
 
 
 
 
AE/SAE Assessment  
 
X& 
X& 
X& 
X 
X 
X 
X 
X 
∞ Prior to study procedures. 
† Prior to study vaccination.  
1 Review results of clinical screening (ESR) or safety laboratory evaluations. 
¬ Review/confirm information or activity in subjects previously consented and screened 
@ Complete medical history will be obtained by interview of subjects at screening (optional) or on Day 1 prior to study 
vaccination and interim medical history will be obtained by interview of subjects at follow-up visits after the study 
vaccination. 
ς   Receipt of non-study influenza vaccines will be solicited through approximately 180 days after the study vaccination, 
and reported in the eCRF. 
*     Not required if done at the optional screening visit. 
√ All current medications and medications taken within 60 days prior to signing the ICF. 
$ Vital signs assessed on Day 1 prior to the 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. 
3 At the screening (or baseline if not done at screening) visit, a physical examination will be performed on all subjects 
to include the following organs and organ systems: skin, head and neck, lungs, heart, liver, spleen, extremities, lymph 
nodes, and nervous system. 
{} Targeted physical examination if indicated based on review of interim medical history. 
^ May be performed on all women of childbearing potential at screening (optional) and will be performed within 24 
hours prior to study vaccination and results must be negative. 
≠ To be performed locally by the site. The ESR value must be confirmed as <30 mm/hr prior to randomization and study 
vaccination. 
~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr. 
4 For subjects who have consented to collected of serum for future use. 
&  Inclusive of reactogenicity assessments performed on the day of vaccination through 7 days after study vaccination. 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 52 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 7: 
Schedule of Study Procedures – Group 3: Early Termination and Unscheduled Visits 
 
Study Visit Number 
 
Early Termination (if 
needed) 
Unscheduled (if 
needed) 
Study Day post dose 
Medical History@ 
X 
X (if indicated) 
Concomitant Medications 
X (if within 21 days after last study 
vaccination and receipt of any non-
study influenza vaccine will be 
recorded if within 180 days after the 
2nd study vaccination) 
X (if within 21 days after last study 
vaccination and receipt of any non-
study influenza vaccine will be 
recorded if within 180 days after the 
2nd study) 
Vital Signs 
(Oral Temperature%, Pulse, and BP) 
X (may be obtained if indicated) 
X (may be obtained if indicated) 
Physical Examination3 
{X} 
{X} 
Venous Blood Collection for Clinical 
Safety Laboratory Evaluations~ 
X (if within 7 days after the last study 
vaccination) 
X (if indicated) 
Venous Blood Collection for  
Immunogenicity  Assays 
X (if within 21 days after last study 
vaccination) 
X (if within 21 days after last study 
vaccination) 
Serum Sample Collected for Future 
Research4 
X(if within 21 days after last study 
vaccination 
X(if within 21 days after last study 
vaccination 
Examine Vaccination Site 
X (if within 7 days after last study 
vaccination) 
X (if within 7 days after last study 
vaccination) 
Post-Administration Reactogenicity 
Assessments 
X (if within 7 days after last study 
vaccination) 
X (if within 7 days after last study 
vaccination) 
Review Memory Aid 
X (if within 7 days after last study 
vaccination) 
X (if within 7 days after last study 
vaccination) 
AE/SAE Assessment  
X& 
X& 
@ Complete medical history will be obtained by interview of subjects at screening (optional) or on Day 1 prior to study 
vaccination and interim medical history will be obtained by interview of subjects at follow-up visits after the study 
vaccination. 
$ Vital signs assessed on Day 1 prior to the 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. 
{} Targeted physical examination if indicated based on review of interim medical history. 
~ Includes WBC, Hgb, PLT, ALT, T. Bili, Cr. 
4 For subjects who have consented to collected of serum for future use. 
& Inclusive of reactogenicity assessments performed on the day of vaccination through 7 days after study vaccination.  


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9.7.1 Sample Size 
Table 8: 
Power (%) to Detect Safety Events  
Event 
Frequency 
N = 30 
N = 60 
N = 120 
≥10% 
Very Common 
96 
>99 
>99 
≥1% 
Common 
26 
45 
70 
≥0.1% 
Uncommon 
3 
6 
11 
≥0.01% 
Rare 
<1 
<1 
1 
 
Table 9: 
Precisions of Binomial Confidence Intervals 
N 
95% CI 
30 
31-69 
60 
37-63 
120 
40-60 
 
Table 10: Objective 1 -Minimum Detectable Difference in Proportion Responders with 80% 
Power (N = 50 per group) 
Assumed Proportion Responders  
comparator arm (pc) 
Minimum detectable difference 
in response rate (pc – pe) 
0.50 
0.27 
0.60 
0.27 
0.70 
0.27 
0.80 
0.26 
0.90 
0.22 
 
 
 


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Table 11: Objective 2 - Minimum Detectable Difference in Proportion Responders with 80% 
Power 
Assumed  
Proportion Responders  
comparator arm (pc) 
Minimum detectable decrease in response 
rate 
(pc - pe) 
0.40 
0.23 
0.50 
0.24 
0.60 
0.25 
0.70 
0.25 
0.80 
0.23 
0.90 
0.20 


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10.2 
Protocol Deviations 
Table 12: Distribution of Protocol Deviations by Category, Type and Treatment Group, All 
Enrolled Subjects 
Category 
Deviation Type 
Group 1: 
Simultaneous 
Administration 
(N=X) 
Group 2: 
Sequential 
Administration  
(N=X) 
Group 3: 
IIV4 Only 
(N=X) 
All Subjects 
(N=X) 
# 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 
 
Met exclusion criterion 
 
 
 
 
 
 
 
 
 
ICF not signed prior to 
study procedures 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
Treatment administration 
schedule 
Any type 
 
 
 
 
 
 
 
 
 
Out of window visit 
 
 
 
 
 
 
 
 
 
Missed visit/visit not 
conducted 
 
 
 
 
 
 
 
 
 
Missed treatment 
administration 
 
 
 
 
 
 
 
 
 
Delayed treatment 
administration 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
Follow-up visit schedule 
Any type 
 
 
 
 
 
 
 
 
 
Out of window visit 
 
 
 
 
 
 
 
 
 
Missed visit/visit not 
conducted 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
Protocol 
procedure/assessment 
Any type 
 
 
 
 
 
 
 
 
 
Incorrect version of ICF 
signed 
 
 
 
 
 
 
 
 
 
Blood not collected 
 
 
 
 
 
 
 
 
 
Too few aliquots 
obtained 
 
 
 
 
 
 
 
 
 
Specimen result not 
obtained 
 
 
 
 
 
 
 
 
 
Required procedure not 
conducted 
 
 
 
 
 
 
 
 
 
Required procedure done 
incorrectly 
 
 
 
 
 
 
 
 


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Table 12: 
Distribution of Protocol Deviations by Category, Type and Treatment group, All 
Enrolled Subjects (continued) 
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Category 
Deviation Type 
Group 1: 
Simultaneous 
Administration 
(N=X) 
Group 2: 
Sequential 
Administration  
(N=X) 
Group 3: 
IIV4 Only 
(N=X) 
All Subjects 
(N=X) 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
 
Study product 
temperature excursion 
 
 
 
 
 
 
 
 
 
Specimen temperature 
excursion 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
Treatment administration Any type 
 
 
 
 
 
 
 
 
 
Required procedure done 
incorrectly 
 
 
 
 
 
 
 
 
 
Study product 
temperature excursion 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
N = Number of subjects enrolled 
 
 


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12.2.2 Displays of Adverse Events 
Table 13: 
Solicited Adverse Event Grading Scale – Local 
Local (Injection Site) Reactogenicity Grading 
Local (Injection 
Site) Reaction 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Pain – experienced 
without touching the 
injection site 
(spontaneous 
discomfort) 
Subject is aware of pain, 
but it does not interfere 
with daily activity, and 
no pain medication is 
taken 
Subject is aware of pain; 
there is interference with 
daily activity or it 
requires repeated use of 
a non-narcotic pain 
reliever for >24 hours 
Subject is aware of pain, 
and it prevents daily 
activity or requires any use 
of a narcotic pain reliever 
Tenderness – hurts only 
when injection site is 
touched or the arm is 
moved 
The area immediately 
surrounding the 
injection site hurts only 
when touched or with 
arm motion, and it does 
not interfere with daily 
activity 
The area immediately 
surrounding the 
injection site hurts when 
touched or with arm 
motion, and it interferes 
with daily activity 
The area immediately 
surrounding the injection 
site hurts when touched or 
with arm motion, and it 
prevents daily activity 
Pruritus (Itching) 
Does not interfere with 
daily activity 
Interferes with daily 
activity 
Prevents daily activity 
Ecchymosis 
(Bruising)* 
Does not interfere with 
daily activity 
Interferes with daily 
activity 
Prevents daily activity 
Erythema (Redness)* 
Does not interfere with 
daily activity 
Interferes with daily 
activity 
Prevents daily activity 
Induration 
(Hardness)/Swelling* 
Does not interfere with 
daily activity 
Interferes with daily 
activity 
Prevents daily activity 
Local (Injection Site) Reactogenicity Measurements 
Local (Injection Site) 
Reaction 
Small (Grade 1) 
Medium (Grade 2) 
Large (Grade 3) 
Ecchymosis 
(Bruising)* 
<20 mm 
20 mm – 50 mm 
>50 mm 
Erythema (Redness)* 
<20 mm 
20 mm – 50 mm 
>50 mm 
Induration 
(Hardness)/Swelling* 
<20 mm 
20 mm – 50 mm 
>50 mm 


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Table 14: 
Solicited Adverse Event Grading Scale - Systemic 
Subjective Systemic Reactogenicity Grading 
Systemic (Subjective) 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Feverishness 
(Chills/Shivering/Sweating) 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Fatigue (Tiredness) 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Malaise (General Unwell 
Feeling) 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Myalgia (Body 
Aches/Muscular Pain)* 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Arthralgia (Joint Pain)* 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Headache 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Nausea 
No interference 
with daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Quantitative Systemic Reactogenicity Grading 
Systemic (Quantitative) 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Fever# - oral† 
38.0°C – 38.4°C 
100.4°F – 101.1°F 
38.5°C – 38.9°C 
101.2°F – 102.0°F 
>38.9°C 
>102.0°F 
*  Not at injection site. 
#  Oral temperature assessed on Day 1 prior to the first study vaccination will be considered as baseline. A 
fever can be considered not related to the study product if an alternative etiology can be documented. 
 


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Table 15: 
Vital Signs Adverse Event Grading Scale 
For Individuals 19-64 years of age, pulse and blood pressure# will be graded as follows: 
Physiologic Parameter 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Bradycardia - beats per minute 
45 – 46 
40 – 44 
<40 
Tachycardia - beats per minute 
101 – 130 
131 – 155 
>155 
Hypotension (systolic) mmHg 
80 – 84 
75 – 79 
<75 
Hypotension (diastolic) mmHg 
50 – 54 
45 – 49 
<45 
Hypertension (systolic) mmHg 
151 – 155 
156 – 160 
>160 
Hypertension (diastolic) mmHg 
96 – 100 
101 – 105 
>105 
# Pulse and blood pressure assessed on Day 1 prior to the first study vaccination will be considered as baseline. 
 


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12.4.1 Individual Laboratory Measurements and Abnormal Laboratory Values 
Table 16: 
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 17: 
Ineligibility Summary of Screen Failures* 
Inclusion/Exclusion Category 
Inclusion/Exclusion Criterion 
na 
%b 
Inclusion and Exclusion 
Number of subjects failing any eligibility 
criterion 
x 
x 
Inclusion 
Any inclusion criterion 
x 
x 
 
[inclusion criterion 1] 
x 
x 
 
[inclusion criterion 2] 
x 
x 
 
[inclusion criterion 3] 
x 
x 
Exclusion 
Any exclusion criterion 
x 
x 
 
[exclusion criterion 1] 
x 
x 
 
[exclusion criterion 2] 
x 
x 
 
[exclusion criterion 3] 
x 
x 
aMore than one criterion may be marked per subject. 
bDenominator for percentages is the total number of screen failures. 
 


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Table 18: 
Analysis Populations by Treatment Group – All Enrolled Subjects* 
Analysis Populations 
Reason Subjects Excluded 
Group 1: 
Simultaneous 
Administration 
(N=X) 
Group 2: 
Sequential 
Administration  
(N=X) 
Group 3: 
IIV4 Only 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
Safety Population 
Any Reason 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Study Dose 1 Not Received 
 
 
 
 
 
 
 
 
Modified Intent to Treat 
Any Reason 
 
 
 
 
 
 
 
 
 
Study Dose 1 Not Received 
 
 
 
 
 
 
 
 
 
No Baseline Results Available 
 
 
 
 
 
 
 
 
 
No Post-Vaccination Results Available 
 
 
 
 
 
 
 
 
Per-Protocol, All Visits 
Found to be Ineligible After Baseline 
 
 
 
 
 
 
 
 
Per-Protocol, Day 22 
Any Reason 
 
 
 
 
 
 
 
 
 
Study Dose 1 Not Received 
 
 
 
 
 
 
 
 
 
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 29 
Any Reason 
 
 
 
 
NA 
NA 
 
 
 
Study Dose 1 Not Received 
 
 
 
 
NA 
NA 
 
 
 
Study Dose 2 Not Received 
 
 
 
 
NA 
NA 
 
 
 
Study Dose 2 Out of Window 
 
 
 
 
NA 
NA 
 
 
 
No Baseline Results Available 
 
 
 
 
NA 
NA 
 
 


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Table 18: Analysis Populations by Treatment Arm – All Enrolled Subjects * (continued) 
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No Day 29 Result Reported by Lab 
 
 
 
 
NA 
NA 
 
 
 
Lost to Follow-up Before Day 29 
 
 
 
 
NA 
NA 
 
 
 
Receipt of Non-Study Vaccination 
 
 
 
 
NA 
NA 
 
 
 
Receipt of Immunosuppressive medication 
 
 
 
 
NA 
NA 
 
 
 
Day 29 Visit Out of Window 
 
 
 
 
NA 
NA 
 
 
Per-Protocol, Day 43 
Any Reason 
 
 
 
 
NA 
NA 
 
 
 
Study Dose 1 Not Received 
 
 
 
 
NA 
NA 
 
 
 
Study Dose 2 Not Received 
 
 
 
 
NA 
NA 
 
 
 
Study Dose 2 Out of Window 
 
 
 
 
NA 
NA 
 
 
 
Study Dose 3 Not Received 
NA 
NA 
 
 
NA 
NA 
 
 
 
Study Dose 3 Out of Window 
NA 
NA 
 
 
NA 
NA 
 
 
 
No Baseline Results Available 
 
 
 
 
NA 
NA 
 
 
 
No Day 43 Result Reported by Lab 
 
 
 
 
NA 
NA 
 
 
 
Lost to Follow-up Before Day 43 
 
 
 
 
NA 
NA 
 
 
 
Receipt of Non-Study Vaccination 
 
 
 
 
NA 
NA 
 
 
 
Receipt of Immunosuppressive medication 
 
 
 
 
NA 
NA 
 
 
 
Day 43 Visit Out of Window 
 
 
 
 
NA 
NA 
 
 
Per-Protocol, Day 64 
Any Reason 
NA 
NA 
 
 
NA 
NA 
 
 
 
Study Dose 1 Not Received 
NA 
NA 
 
 
NA 
NA 
 
 
 
Study Dose 2 Not Received 
NA 
NA 
 
 
NA 
NA 
 
 
 
Study Dose 2 Out of Window 
NA 
NA 
 
 
NA 
NA 
 
 
 
Study Dose 3 Not Received 
NA 
NA 
 
 
NA 
NA 
 
 
 
Study Dose 3 Out of Window 
NA 
NA 
 
 
NA 
NA 
 
 


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Table 18: Analysis Populations by Treatment Arm – All Enrolled Subjects * (continued) 
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No Baseline Results Available 
NA 
NA 
 
 
NA 
NA 
 
 
 
No Day 64 Result Reported by Lab 
NA 
NA 
 
 
NA 
NA 
 
 
 
Lost to Follow-up Before Day 64 
NA 
NA 
 
 
NA 
NA 
 
 
 
Receipt of Non-Study Vaccination 
NA 
NA 
 
 
NA 
NA 
 
 
 
Receipt of Immunosuppressive medication 
NA 
NA 
 
 
NA 
NA 
 
 
Per-Protocol, Day 181 
Any Reason 
 
 
 
 
 
 
 
 
 
Study Dose 1 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 
 
 
 
 
 
 
 
 
Per Protocol, Day 202 
Any Reason 
 
 
NA 
NA 
NA 
NA 
 
 
 
Study Dose 2 Not Received 
 
 
NA 
NA 
NA 
NA 
 
 
 
Study Dose 2 Out of Window 
 
 
 
 
 
 
 
 
 
No Baseline Results Available 
 
 
NA 
NA 
NA 
NA 
 
 
 
No Day 202 Result Reported by Lab 
 
 
NA 
NA 
NA 
NA 
 
 
 
Lost to Follow-up Before Day 202 
 
 
NA 
NA 
NA 
NA 
 
 
 
Receipt of Non-Study Vaccination 
 
 
NA 
NA 
NA 
NA 
 
 
 
Receipt of Immunosuppressive medication 
 
 
NA 
NA 
NA 
NA 
 
 
Per Protocol, Day 223 
Any Reason 
NA 
NA 
 
 
NA 
NA 
 
 
 
Study Dose 3 Not Received 
NA 
NA 
 
 
NA 
NA 
 
 
 
Study Dose 3 Out of Window 
NA 
NA 
 
 
NA 
NA 
 
 


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Table 18: Analysis Populations by Treatment Arm – All Enrolled Subjects * (continued) 
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No Baseline Results Available 
NA 
NA 
 
 
NA 
NA 
 
 
 
No Day 223 Result Reported by Lab 
NA 
NA 
 
 
NA 
NA 
 
 
 
Lost to Follow-up Before Day 223 
NA 
NA 
 
 
NA 
NA 
 
 
 
Receipt of Non-Study Vaccination 
NA 
NA 
 
 
NA 
NA 
 
 
 
Receipt of Immunosuppressive medication 
NA 
NA 
 
 
NA 
NA 
 
 
N=Number of subjects enrolled 
 


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Table 19: 
Subject Disposition by Treatment Group, All Enrolled Subjects* 
Subject 
Disposition 
Group 1: 
Simultaneous 
Administration 
(N=X) 
Group 2: 
Sequential Administration 
(N=X) 
Group 3: 
IIV4 Only 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
Screened 
x 
-- 
x 
-- 
x 
-- 
x 
-- 
Enrolled/Randomized 
x 
100 
x 
100 
x 
100 
x 
100 
Received Dose 1 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Received Dose 2 
x 
xx 
x 
xx 
NA 
NA 
x 
xx 
Received Dose 3 
NA 
NA 
x 
xx 
NA 
NA 
x 
xx 
Received All Scheduled Doses a 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Completed Blood Draw for Primary Immunogenicity 
Analysisb 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Included in Per Protocol Primary Immunogenicity Analysisb c 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Completed Primary Follow-upa b c 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Completed Final Study Visit  
x 
xx 
x 
xx 
x 
xx 
x 
xx 
N=Number of subjects enrolled 
aRefer to Listing 2 for reasons subjects discontinued from study vaccinations or terminated early. 
bThe final blood draw for Primary Immunogenicity Analysis occurs at 21 days post final dose (Day 43 for Group 1; Day 64 for Group 2; Day 21 for Group 3). 
cRefer to Listing 5 for reasons subjects are excluded from the per protocol population. 


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Table 20: 
Dates of First Dose by Site and Treatment Group for the Safety Analysis Population 
Dates of Dosing 
Group 1: 
Simultaneous 
Administration 
(N=X) 
Group 2: 
Sequential 
Administration  
(N=X) 
Group 3: 
IIV4 Only 
(N=X) 
All Subjects 
(N=X) 
[Site 1] 
Total (Entire period of enrollment) 
x 
x 
x 
x 
DDMMMYYYY-DDMMMYYYY 
x 
x 
x 
x 
…. 
 
 
 
 
[Site 2] 
Total (Entire period of enrollment) 
x 
x 
x 
x 
DDMMMYYYY-DDMMMYYYY 
x 
x 
x 
x 
…. 
 
 
 
 
[Repeat for all sites] 
N= Number of subjects in the Safety population. 
 
Table with similar format: 
Table 21: 
Dates of Second Dose by Site and Treatment Group for the Safety Analysis Population 
Table 22: 
Dates of Third Dose by Site and Treatment Group for the Safety Analysis Population 
 
 


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14.1.2 Demographic Data 
Table 23: 
Summary of Categorical Demographic and Baseline Characteristics by Site, All Enrolled Subjects 
Variable 
Characteristic 
[Site 1] 
(N=X) 
[Site 2] 
(N=X) 
[Site 3] 
(N=X) 
[Site 4] 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Sex  
Male 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Female 
 
 
 
 
 
 
 
 
 
 
BMI 
< 30 
 
 
 
 
 
 
 
 
 
 
 
≥ 30 
 
 
 
 
 
 
 
 
 
 
Ethnicity  
Not Hispanic or Latino 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Hispanic or Latino 
 
 
 
 
 
 
 
 
 
 
 
Not Reported 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
Race  
American Indian or Alaska Native 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Asian 
 
 
 
 
 
 
 
 
 
 
 
Native Hawaiian or Other Pacific Islander 
 
 
 
 
 
 
 
 
 
 
 
Black or African American 
 
 
 
 
 
 
 
 
 
 
 
White 
 
 
 
 
 
 
 
 
 
 
 
Multi-Racial 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
Prior Seasonal Influenza Vaccination 
Received 2016-2017 
 
 
 
 
 
 
 
 
 
 
 
Did not receive 2016-2017 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
N= Number of subjects enrolled 
 


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Table 24: 
Summary of Continuous Demographic and Baseline Characteristics by Site, All Enrolled Subjects 
Variable 
Statistic 
[Site 1] 
(N=X) 
[Site 2] 
(N=X) 
[Site 3] 
(N=X) 
[Site 4] 
(N=X) 
All Subjects 
(N=X) 
Age 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Standard Deviation 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
x 
x 
 
Maximum 
x 
x 
x 
x 
x 
BMI 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Standard Deviation 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
x 
x 
 
Maximum 
x 
x 
x 
x 
x 
N= Number of subjects enrolled 
 


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Table 25: 
Summary of Categorical Demographic and Baseline Characteristics by Treatment Group, All Enrolled Subjects* 
Variable 
Characteristic 
Group 1: 
Simultaneous 
Administration 
(N=X) 
Group 2: 
Sequential 
Administration  
(N=X) 
Group 3: 
IIV4 Only 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
Sex  
Male 
 
 
 
 
 
 
 
 
 
Female 
 
 
 
 
 
 
 
 
BMI 
< 30 
 
 
 
 
 
 
 
 
 
≥ 30 
 
 
 
 
 
 
 
 
Ethnicity  
Not Hispanic or Latino 
 
 
 
 
 
 
 
 
 
Hispanic or Latino 
 
 
 
 
 
 
 
 
 
Not Reported 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
Race  
American Indian or Alaska Native 
 
 
 
 
 
 
 
 
 
Asian 
 
 
 
 
 
 
 
 
 
Native Hawaiian or Other Pacific Islander 
 
 
 
 
 
 
 
 
 
Black or African American 
 
 
 
 
 
 
 
 
 
White 
 
 
 
 
 
 
 
 
 
Multi-Racial 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
Prior Seasonal Influenza 
Vaccination 
Received 2016-2017 
 
 
 
 
 
 
 
 
 
Did not receive 2016-2017 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
N=Number of subjects enrolled 


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Table 26: 
Summary of Continuous Baseline Characteristics by Treatment Group, All Enrolled Subjects* 
Variable 
Statistic 
Group 1 
Simultaneous 
Administration 
(N=X) 
Group 2 
Sequential Administration  
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
All Subjects 
(N=X) 
Age 
Mean 
x.x 
x.x 
x.x 
x.x 
 
Standard Deviation 
x.x 
x.x 
x.x 
x.x 
 
Median 
x 
x 
x 
x 
 
Minimum 
x 
x 
x 
x 
 
Maximum 
x 
x 
x 
x 
BMI 
Mean 
x.x 
x.x 
x.x 
x.x 
 
Standard Deviation 
x.x 
x.x 
x.x 
x.x 
 
Median 
x 
x 
x 
x 
 
Minimum 
x 
x 
x 
x 
 
Maximum 
x 
x 
x 
x 
N=Number of subjects enrolled. 
 


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14.1.3 Summary of Prior or Concurrent Medical Conditions 
Table 27: 
Summary of Subjects with Prior or Concurrent Medical Conditions by MedDRA® System Organ Class and Treatment 
Group, Safety Analysis Population 
MedDRA® System Organ Class 
Group 1: 
Simultaneous Administration 
(N=X) 
Group 2: 
Sequential Administration  
(N=X) 
Group 3: 
IIV4 Only 
(N=X) 
n 
% 
n 
% 
n 
% 
Any SOC 
x 
xx 
x 
xx 
x 
xx 
[SOC 1] 
x 
xx 
x 
xx 
x 
xx 
[SOC 2] 
x 
xx 
x 
xx 
x 
xx 
… 
 
 
 
 
 
 
Note: N=Number of subjects in the Safety population;  
n = Number of subjects reporting medical history within the specified SOC. A subject is only counted once per SOC. 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 73 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.2 
Immunogenicity Tables 
14.2.1 Immune Response Against Vaccine Strains 
Table 28: 
Summaries of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study Day and Treatment Group, Modified 
Intent-to-Treat Population* 
Time Point 
Group 1: 
Simultaneous Administration 
(N=X) 
Group 2: 
Sequential Administration  
(N=X) 
Group 3: 
IIV4 Only 
(N=X) 
Baseline (Pre-Dose 1) 
 
 
 
n 
x 
x 
x 
GMT (95% CI) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
Titer ≥ 1:40 - %(95% CI) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
21 Days Post Dose 1 
 
 
 
n 
x 
x 
x 
GMT (95% CI) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
Seroconversion - % (95% CI) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Titer ≥ 1:40 - % (95% CI) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
21 Days Post Dose 2 
 
 
 
n 
x 
x 
NA 
GMT (95% CI) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
NA 
Seroconversion - % (95% CI) 
xx (xx, xx) 
xx (xx, xx) 
NA 
Titer ≥ 1:40 - % (95% CI) 
xx (xx, xx) 
xx (xx, xx) 
NA 
21 Days Post Dose 3 
 
 
 
n 
NA 
x 
NA 
GMT (95% CI) 
NA 
xxx.x (xxx.x,xxx.x) 
NA 
Seroconversion - % (95% CI) 
NA 
xx (xx, xx) 
NA 
Titer ≥ 1:40 - % (95% CI) 
NA 
xx (xx, xx) 
NA 
180 Days Post Dose 1 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
Table 28: Summaries of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study Day and Treatment Group, Modified 
Intent-to-Treat Population (continued) 
- 74 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Time Point 
Group 1: 
Simultaneous Administration 
(N=X) 
Group 2: 
Sequential Administration  
(N=X) 
Group 3: 
IIV4 Only 
(N=X) 
n 
x 
x 
x 
GMT (95% CI) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
Seroconversion - % (95% CI) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Titer ≥ 1:40 - % (95% CI) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
180 Days Post Second Dose of AS03-adjuvanted H7N9 
Vaccine a 
 
 
 
n 
x 
x 
NA 
GMT (95% CI) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
NA 
Seroconversion - % (95% CI) 
xx (xx, xx) 
xx (xx, xx) 
NA 
Titer ≥ 1:40 - % (95% CI) 
xx (xx, xx) 
xx (xx, xx) 
NA 
N=number of subjects in the Modified Intent to Treat population; n = number of subjects with available results; GMT = Geometric Mean Titer 
a 180 days post second AS03-adjuvanted H7N9 vaccine administration varies by group (Day 202 for Group 1, Day 223 for Group 2, NA for Group 3). 
Tables with similar format 
Table 29: Summaries of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study Day and Treatment Group, Per Protocol 
Population* 
Table 30: Summaries of Neutralizing Antibody Against 2017 A/H7N9 by Study Day and Treatment Group, Modified Intent-to-Treat 
Population* 
Table 31: 
Summaries of Neutralizing Antibody Against 2017 A/H7N9 by Study Day and Treatment Group, Per Protocol Population* 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 75 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 32: 
Summaries of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains by Study Day and Treatment Group, 
Modified Intent-to-Treat Population* 
Time Point 
A/Michigan/45/2015 X-275 
(H1N1) 
A/Hong Kong/4801/2014 X263B 
(H3N2) 
B/Phuket/3073/2013  
(B Yamagata lineage) 
B/Brisbane/60/2008  
(B Victoria lineage) 
Group 1 
Sim. 
Admin. 
(N=X) 
Group 2 
Seq. 
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Group 1 
Sim. 
Admin. 
(N=X) 
Group 2 
Seq. 
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Group 1 
Sim. 
Admin. 
(N=X) 
Group 2 
Seq. 
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Group 1 
Sim. 
Admin. 
(N=X) 
Group 2 
Seq. 
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Baseline  
(Pre-Dose 1) 
 
 
 
 
 
 
 
 
 
 
 
 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GMT  
(95% CI) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x 
,xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
Titer ≥ 1:40 - 
% (95% CI) 
xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) 
21 Days Post 
Dose 1 
 
 
 
 
 
 
 
 
 
 
 
 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GMT  
(95% CI) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
Seroconversion 
% (95% CI) 
xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) 
Titer ≥ 1:40 - % 
(95% CI) 
xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) 
21 Days Post 
Dose 2 
 
 
 
 
 
 
 
 
 
 
 
 
n 
x 
x 
NA 
x 
x 
NA 
x 
x 
NA 
x 
x 
NA 
GMT  
(95% CI) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
NA 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
NA 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
NA 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
NA 
Seroconversion 
% (95% CI) 
xx (xx, xx) xx (xx, xx) 
NA 
xx (xx, xx) xx (xx, xx) 
NA 
xx (xx, xx) xx (xx, xx) 
NA 
xx (xx, xx) xx (xx, xx) 
NA 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
Table 32: Summaries of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains by Study Day and Treatment Group, 
Modified Intent-to-Treat Population (continued) 
- 76 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Time Point 
A/Michigan/45/2015 X-275 
(H1N1) 
A/Hong Kong/4801/2014 X263B 
(H3N2) 
B/Phuket/3073/2013  
(B Yamagata lineage) 
B/Brisbane/60/2008  
(B Victoria lineage) 
Group 1 
Sim. 
Admin. 
(N=X) 
Group 2 
Seq. 
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Group 1 
Sim. 
Admin. 
(N=X) 
Group 2 
Seq. 
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Group 1 
Sim. 
Admin. 
(N=X) 
Group 2 
Seq. 
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Group 1 
Sim. 
Admin. 
(N=X) 
Group 2 
Seq. 
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Titer ≥ 1:40 - % 
(95% CI) 
xx (xx, xx) xx (xx, xx) 
NA 
xx (xx, xx) xx (xx, xx) 
NA 
xx (xx, xx) xx (xx, xx) 
NA 
xx (xx, xx) xx (xx, xx) 
NA 
21 Days Post 
Dose 3 
 
 
 
 
 
 
 
 
 
 
 
 
n 
NA 
x 
NA 
NA 
x 
NA 
NA 
x 
NA 
NA 
x 
NA 
GMT  
(95% CI) 
NA 
xxx.x 
(xxx.x,xxx.
x) 
NA 
NA 
xxx.x 
(xxx.x,xxx.
x) 
NA 
NA 
xxx.x 
(xxx.x,xxx.
x) 
NA 
NA 
xxx.x 
(xxx.x,xxx.
x) 
NA 
Seroconversion 
% (95% CI) 
NA 
xx (xx, xx) 
NA 
NA 
xx (xx, xx) 
NA 
NA 
xx (xx, xx) 
NA 
NA 
xx (xx, xx) 
NA 
Titer ≥ 1:40 - % 
(95% CI) 
NA 
xx (xx, xx) 
NA 
NA 
xx (xx, xx) 
NA 
NA 
xx (xx, xx) 
NA 
NA 
xx (xx, xx) 
NA 
180 Days Post 
Dose 1 (IIV4) 
 
 
 
 
 
 
 
 
 
 
 
 
n 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
GMT  
(95% CI) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
Seroconversion 
% (95% CI) 
xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) 
Titer ≥ 1:40 - % 
(95% CI) 
xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
Table 32: Summaries of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains by Study Day and Treatment Group, 
Modified Intent-to-Treat Population (continued) 
- 77 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Time Point 
A/Michigan/45/2015 X-275 
(H1N1) 
A/Hong Kong/4801/2014 X263B 
(H3N2) 
B/Phuket/3073/2013  
(B Yamagata lineage) 
B/Brisbane/60/2008  
(B Victoria lineage) 
Group 1 
Sim. 
Admin. 
(N=X) 
Group 2 
Seq. 
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Group 1 
Sim. 
Admin. 
(N=X) 
Group 2 
Seq. 
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Group 1 
Sim. 
Admin. 
(N=X) 
Group 2 
Seq. 
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Group 1 
Sim. 
Admin. 
(N=X) 
Group 2 
Seq. 
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
180 Days Post 
Second Dose of 
AS03-
adjuvanted 
H7N9 
Vaccinea 
 
 
 
 
 
 
 
 
 
 
 
 
n 
x 
x 
NA 
x 
x 
NA 
x 
x 
NA 
x 
x 
NA 
GMT  
(95% CI) 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
NA 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
NA 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
NA 
xxx.x 
(xxx.x,xxx.
x) 
xxx.x 
(xxx.x,xxx.
x) 
NA 
Seroconversion 
% (95% CI) 
xx (xx, xx) xx (xx, xx) 
NA 
xx (xx, xx) xx (xx, xx) 
NA 
xx (xx, xx) xx (xx, xx) 
NA 
xx (xx, xx) xx (xx, xx) 
NA 
Titer ≥ 1:40 - % 
(95% CI) 
xx (xx, xx) xx (xx, xx) 
NA 
xx (xx, xx) xx (xx, xx) 
NA 
xx (xx, xx) xx (xx, xx) 
NA 
xx (xx, xx) xx (xx, xx) 
NA 
N=number of subjects in the Modified Intent to Treat population; n = number of subjects with available results; GMT = Geometric Mean Titer 
a 180 days post second AS03-adjuvanted H7N9 vaccine administration varies by group (Day 202 for Group 1, Day 223 for Group 2, NA for Group 3). 
Tables with similar format 
Table 33: Summaries of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains by Study Day and Treatment Group, Per 
Protocol Population* 
Table 34: Summaries of Neutralizing Antibody Against Seasonal IIV4 Strains by Study Day and Treatment Group, Modified Intent-to-
Treat Population* 
Table 35: Summaries of Neutralizing Antibody Against Seasonal IIV4 Strains by Study Day and Treatment Group, Per Protocol 
Population* 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 78 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 36: Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Treatment Group and Age Group at 21 Days 
Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per-Protocol Population* 
 
Group 1: 
Simultaneous Administration 
(N=X) 
Group 2: 
Sequential Administration  
(N=X) 
Age 19-34 years 
 
 
 n  
x 
x 
 GMT (95% CI) 
xxx.x(xxx.x,xxx.x) 
xxx.x(xxx.x,xxx.x) 
 Seroconversion - %(95% CI) 
xx (xx, xx) 
xx (xx, xx) 
 Titer ≥ 1:40 - %(95% CI) 
xx (xx, xx) 
xx (xx, xx) 
Age 35-49 years 
 
 
 n  
x 
x 
 GMT (95% CI) 
xxx.x(xxx.x,xxx.x) 
xxx.x(xxx.x,xxx.x) 
 Seroconversion - %(95% CI) 
xx (xx, xx) 
xx (xx, xx) 
 Titer ≥ 1:40 - %(95% CI) 
xx (xx, xx) 
xx (xx, xx) 
Age 50-64 years 
 
 
 n  
x 
x 
 GMT (95% CI) 
xxx.x(xxx.x,xxx.x) 
xxx.x(xxx.x,xxx.x) 
 Seroconversion - %(95% CI) 
xx (xx, xx) 
xx (xx, xx) 
 Titer ≥ 1:40 - %(95% CI) 
xx (xx, xx) 
xx (xx, xx) 
N = Number of subjects in the Per Protocol Population; n = number of subjects with results reported 
Tables with similar format: 
Table 37: Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Treatment Group and Age Group at 180 Days 
Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per-Protocol Population 
Table 38: Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Group and Age Group at 21 Days Post Second Dose of 
AS03 adjuvanted A/H7N9 Vaccine, Per-Protocol Population* 
Table 39: Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Group and Age Group at 180 Days Post Second Dose 
of AS03 adjuvanted A/H7N9 Vaccine, Per-Protocol Population 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 79 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 40: Summary of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains by Treatment Group and Age Group at 21 
Days Post IIV4, Per-Protocol Population* 
 
A/Michigan/45/2015 X-275 
(H1N1) 
A/Hong Kong/4801/2014 X263B 
(H3N2) 
B/Phuket/3073/2013  
(B Yamagata lineage) 
B/Florida/04/2006  
(Yamagata lineage) 
Group 1 
Sim. 
Admin. 
(N=X) 
Group 2 
Seq. 
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Group 1 
Sim. 
Admin. 
(N=X) 
Group 2 
Seq. 
Admin. 
(N=X) 
Group 3 
IIV4 
Only 
(N=X) 
Group 1 
Sim. 
Admin. 
(N=X) 
Group 2 
Seq. 
Admin. 
(N=X) 
Group 3 
IIV4 
Only 
(N=X) 
Group 1 
Sim. 
Admin. 
(N=X) 
Group 2 
Seq. 
Admin. 
(N=X) 
Group 3 
IIV4 
Only 
(N=X) 
Age  
19-34 years 
 
 
 
 
 
 
 
 
 
 
 
 
 n  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 GMT  
(95% CI) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
 
Seroconversi
on - %(95% 
CI) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
 Titer ≥ 1:40 - 
%(95% CI) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
Age  
35-49 years 
 
 
 
 
 
 
 
 
 
 
 
 
 n  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 GMT (95% 
CI) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
 
Seroconversi
on - %(95% 
CI) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
 Titer ≥ 1:40 - 
%(95% CI) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
Age  
50-64 years 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
Table 40: Summary of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains by Treatment Group and Age Group at 21 
Days Post IIV4, Per-Protocol Population (continued) 
- 80 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
 
A/Michigan/45/2015 X-275 
(H1N1) 
A/Hong Kong/4801/2014 X263B 
(H3N2) 
B/Phuket/3073/2013  
(B Yamagata lineage) 
B/Florida/04/2006  
(Yamagata lineage) 
Group 1 
Sim. 
Admin. 
(N=X) 
Group 2 
Seq. 
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Group 1 
Sim. 
Admin. 
(N=X) 
Group 2 
Seq. 
Admin. 
(N=X) 
Group 3 
IIV4 
Only 
(N=X) 
Group 1 
Sim. 
Admin. 
(N=X) 
Group 2 
Seq. 
Admin. 
(N=X) 
Group 3 
IIV4 
Only 
(N=X) 
Group 1 
Sim. 
Admin. 
(N=X) 
Group 2 
Seq. 
Admin. 
(N=X) 
Group 3 
IIV4 
Only 
(N=X) 
 n  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 GMT (95% 
CI) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
 
Seroconversi
on - %(95% 
CI) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
 Titer ≥ 1:40 - 
%(95% CI) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
xx (xx, 
xx) 
N = Number of subjects in the Per Protocol Population; n = number of subjects with results reported 
 
Tables with similar format: 
Table 41: Summary of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains by Treatment Group and Age Group at 180 
Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per-Protocol Population 
Table 42: Summary of Neutralizing Antibody Against Seasonal IIV4 Strains by Treatment Group and Age Group at 21 Days Post 
Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per-Protocol Population* 
Table 43: Summary of Neutralizing Antibody Against Seasonal IIV4 Strains by Treatment Group and Age Group at 180 Days Post 
Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per-Protocol Population 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 44: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Treatment Group and Sex at 21 Days Post 
Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per-Protocol Population* 
 
Group 1: 
Simultaneous Administration 
(N=X) 
Group 2: 
Sequential Administration  
(N=X) 
Female 
 
 
 n  
x 
x 
 GMT (95% CI) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
 Seroconversion - %(95% CI) 
xx (xx, xx) 
xx (xx, xx) 
 Titer ≥ 1:40 - %(95% CI) 
xx (xx, xx) 
xx (xx, xx) 
Male 
 
 
 n  
x 
x 
 GMT (95% CI) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
 Seroconversion - %(95% CI) 
xx (xx, xx) 
xx (xx, xx) 
 Titer ≥ 1:40 - %(95% CI) 
xx (xx, xx) 
xx (xx, xx) 
N = Number of subjects in the Per Protocol Population; n = number of subjects with results reported 
Tables with similar format: 
Table 45: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Treatment Group and Sex at 180 Days Post 
Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per-Protocol Population 
Table 46: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Group and Sex at 21 Days Post Second Dose of AS03 
adjuvanted A/H7N9 Vaccine, Per-Protocol Population* 
Table 47: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Group and Sex at 180 Days Post Second Dose of 
AS03 adjuvanted A/H7N9 Vaccine, Per-Protocol Population 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 82 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 48: 
Summary of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains by Treatment Group and Sex at 21 Days 
Post IIV4 Vaccination, Per-Protocol Population* 
 
A/Michigan/45/2015 X-275 
(H1N1) 
A/Hong Kong/4801/2014 X263B 
(H3N2) 
B/Phuket/3073/2013  
(B Yamagata lineage) 
B/Brisbane/60/2008  
(B Victoria lineage) 
Group 1 
Sim. 
Admin. 
(N=X) 
Group 2 
Seq. 
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Group 1 
Sim.  
Admin. 
(N=X) 
Group 2 
Seq.  
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Group 1 
Sim.  
Admin. 
(N=X) 
Group 2 
Seq.  
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Group 1 
Sim.  
Admin. 
(N=X) 
Group 2 
Seq.  
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Female 
 
 
 
 
 
 
 
 
 
 
 
 
 n  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 GMT  
(95% CI) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
 
Seroconversion 
- %(95% CI) 
xx (xx, xx) xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) 
 Titer ≥ 1:40 - 
%(95% CI) 
xx (xx, xx) xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) 
Male 
 
 
 
 
 
 
 
 
 
 
 
 
 n  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 GMT 
(95% 
CI) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
 
Seroconversion 
- %(95% CI) 
xx (xx, xx) xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) 
 Titer ≥ 1:40 - 
%(95% CI) 
xx (xx, xx) xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) 
N = Number of subjects in the Per Protocol Population; n = number of subjects with results reported 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Tables with similar format: 
Table 49: 
Summary of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains by Treatment Group and Sex at 180 Days 
Post IIV4 Vaccination, Per-Protocol Population 
Table 50: 
Summary of Neutralizing Antibody Against Seasonal IIV4 Strains by Treatment Group and Sex at 21 Days Post IIV4 
Vaccination, Per-Protocol Population* 
Table 51: 
Summary of Neutralizing Antibody Against Seasonal IIV4 Strains by Treatment Group and Sex at 180 Days Post IIV4 
Vaccination, Per-Protocol Population 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 84 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 52: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Treatment Group and BMI at 21 Days Post 
Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per-Protocol Population* 
 
Group 1: 
Simultaneous Administration 
(N=X) 
Group 2: 
Sequential Administration  
(N=X) 
BMI < 30 
 
 
 n  
x 
x 
 GMT (95% CI) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
 Seroconversion - %(95% CI) 
xx (xx, xx) 
xx (xx, xx) 
 Titer ≥ 1:40 - %(95% CI) 
xx (xx, xx) 
xx (xx, xx) 
BMI ≥ 30 
 
 
 n  
x 
x 
 GMT (95% CI) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
 Seroconversion - %(95% CI) 
xx (xx, xx) 
xx (xx, xx) 
 Titer ≥ 1:40 - %(95% CI) 
xx (xx, xx) 
xx (xx, xx) 
N = Number of subjects in the Per Protocol Population; n = number of subjects with results reported 
Tables with similar format: 
Table 53: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Treatment Group and BMI at 180 Days Post 
Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per-Protocol Population 
Table 54: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Group and BMI at 21 Days Post Second Dose of 
AS03 adjuvanted A/H7N9 Vaccine, Per-Protocol Population* 
Table 55: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Group and BMI at 180 Days Post Second Dose of 
AS03 adjuvanted A/H7N9 Vaccine, Per-Protocol Population 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 56: 
Summary of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains by Treatment Group and BMI at 21 Days 
Post IIV4 Vaccination, Per-Protocol Population* 
 
A/Michigan/45/2015 X-275 
(H1N1) 
A/Hong Kong/4801/2014 X263B 
(H3N2) 
B/Phuket/3073/2013  
(B Yamagata lineage) 
B/Brisbane/60/2008  
(B Victoria lineage) 
Group 1 
Sim.  
Admin. 
(N=X) 
Group 2 
Seq.  
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Group 1 
Sim.  
Admin. 
(N=X) 
Group 2 
Seq.  
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Group 1 
Sim.  
Admin. 
(N=X) 
Group 2 
Seq.  
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Group 1 
Sim.  
Admin. 
(N=X) 
Group 2 
Seq.  
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
BMI < 30 
 
 
 
 
 
 
 
 
 
 
 
 
 n  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 GMT  
(95% CI) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
 
Seroconversion 
- %(95% CI) 
xx (xx, xx) xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) 
 Titer ≥ 1:40 - 
%(95% CI) 
xx (xx, xx) xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) 
BMI ≥ 30 
 
 
 
 
 
 
 
 
 
 
 
 
 n  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 GMT 
(95% 
CI) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
 
Seroconversion 
- %(95% CI) 
xx (xx, xx) xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) 
 Titer ≥ 1:40 - 
%(95% CI) 
xx (xx, xx) xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) 
N = Number of subjects in the Per Protocol Population; n = number of subjects with results reported 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 86 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Tables with similar format: 
Table 57: 
Summary of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains by Treatment Group and BMI at 180 Days 
Post IIV4 Vaccination, Per-Protocol Population 
Table 58: 
Summary of Neutralizing Antibody Against Seasonal IIV4 Strains by Treatment Group and BMI at 21 Days Post IIV4 
Vaccination, Per-Protocol Population* 
Table 59: 
Summary of Neutralizing Antibody Against Seasonal IIV4 Strains by Treatment Group and BMI at 180 Days Post IIV4 
Vaccination, Per-Protocol Population 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 87 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 60: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Treatment Group and Prior Seasonal Influenza 
Vaccination at 21 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per-Protocol Population* 
 
Group 1: 
Simultaneous Administration 
(N=X) 
Group 2: 
Sequential  
Administration  
(N=X) 
Did Not Receive 2016-2017 Seasonal Influenza Vaccination 
 
 
 n  
x 
x 
 GMT (95% CI) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
 Seroconversion - %(95% CI) 
xx (xx, xx) 
xx (xx, xx) 
 Titer ≥ 1:40 - %(95% CI) 
xx (xx, xx) 
xx (xx, xx) 
Received 2016-2017 Seasonal Influenza Vaccination 
 
 
 n  
x 
x 
 GMT (95% CI) 
xxx.x (xxx.x,xxx.x) 
xxx.x (xxx.x,xxx.x) 
 Seroconversion - %(95% CI) 
xx (xx, xx) 
xx (xx, xx) 
 Titer ≥ 1:40 - %(95% CI) 
xx (xx, xx) 
xx (xx, xx) 
N = Number of subjects in the Per Protocol Population; n = number of subjects with results reported 
 
Tables with similar format: 
 
Table 61: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Treatment Group and Prior Seasonal Influenza 
Vaccination at 180 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per-Protocol Population 
Table 62: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Group and Prior Seasonal Influenza Vaccination at 
21 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per-Protocol Population* 
Table 63: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Treatment Group and Prior Seasonal Influenza Vaccination at 
180 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per-Protocol Population 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 88 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 64: 
Summary of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains by Treatment Group and Prior Seasonal 
Influenza Vaccination at 21 Days Post IIV4 Vaccination, Per-Protocol Population* 
 
A/Michigan/45/2015 X-275 
(H1N1) 
A/Hong Kong/4801/2014 X263B 
(H3N2) 
B/Phuket/3073/2013  
(B Yamagata lineage) 
B/Brisbane/60/2008  
(B Victoria lineage) 
Group 1 
Sim.  
Admin. 
(N=X) 
Group 2 
Seq.  
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Group 1 
Sim.  
Admin. 
(N=X) 
Group 2 
Seq.  
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Group 1 
Sim.  
Admin. 
(N=X) 
Group 2 
Seq.  
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Group 1 
Sim.  
Admin. 
(N=X) 
Group 2 
Seq.  
Admin. 
(N=X) 
Group 3 
IIV4 Only 
(N=X) 
Did Not Receive 2016-2017 Seasonal Influenza Vaccination 
 n  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 GMT  
(95% CI) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
 
Seroconversion 
- %(95% CI) 
xx (xx, xx) xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) 
 Titer ≥ 1:40 - 
%(95% CI) 
xx (xx, xx) xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) 
Received 2016-2017 Seasonal Influenza Vaccination 
 n  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 GMT 
(95% 
CI) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
xxx.x 
(xxx.x, 
xxx.x) 
 
Seroconversion 
- %(95% CI) 
xx (xx, xx) xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) 
 Titer ≥ 1:40 - 
%(95% CI) 
xx (xx, xx) xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) xx (xx, xx) 
N = Number of subjects in the Per Protocol Population; n = number of subjects with results reported 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
 
- 89 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Tables with similar format: 
 
Table 65: 
Summary of Hemagglutination Inhibition Antibody Against Seasonal IIV4 Strains by Treatment Group and Prior Seasonal 
Influenza Vaccination at 180 Days Post IIV4 Vaccination, Per-Protocol Population 
Table 66: 
Summary of Neutralizing Antibody Against Seasonal IIV4 Strains by Treatment Group and Prior Seasonal Influenza 
Vaccination at 21 Days Post IIV4 Vaccination, Per-Protocol Population* 
Table 67: 
Summary of Neutralizing Antibody Against Seasonal IIV4 Strains by Treatment Group and Prior Seasonal Influenza 
Vaccination at 180 Days Post IIV4 Vaccination, Per-Protocol Population 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
 
- 90 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 68: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule with HAI Seroconversion Against 2017 
A/H7N9 at 21 Days post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per Protocol Population* 
Model Parameter 
Parameter Category 
Parameter Estimate 
SE 
p-value 
Odds Ratio 
95%CI 
Intercept 
N/A 
xxx.x 
xxx.x 
x.xxx 
- 
- 
Treatment 
 
Simultaneous 
Administration 
(reference) 
- 
- 
- 
- 
- 
Sequential 
Administration 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
N = XX (Number of subjects in the Per Protocol Population) 
n = XX (number of subjects with results available at 21 days post second dose of AS03 adjuvanted A/H7N9 IIV in the per protocol population).  
XX subjects missing covariate data were excluded from this analysis. 
 
Tables with similar format: 
 
Table 69: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule with HAI Seroconversion Against 2017 
A/H7N9 at 180 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per Protocol Population * 
Table 70: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule with Neut Seroconversion Against 2017 
A/H7N9 at 21 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per Protocol Population  
Table 71: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule with Neut Seroconversion Against 2017 
A/H7N9 at 180 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per Protocol Population 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
 
- 91 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 72: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule with HAI Seroconversion Against 
Seasonal IIV4 Strains at 21 Days post IIV4 Vaccination, Per Protocol Population* 
Model Parameter 
Parameter Category 
Parameter Estimate 
SE 
p-value 
Odds Ratio 
95%CI 
A/Michigan/45/2015 X-275 (H1N1) 
Intercept 
N/A 
xxx.x 
xxx.x 
x.xxx 
- 
- 
Treatment 
Simultaneous 
Administration 
(reference) 
- 
- 
- 
- 
- 
 
Sequential 
Administration 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 
IIV4 Only 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
[Repeat for all IIV4 Strains] 
N = XX (Number of subjects in the Per Protocol Population) 
n = XX (number of subjects with results available at 21 days post IIV4 vaccination in the per protocol population).  
XX subjects missing covariate data were excluded from this analysis.  
 
Tables with similar format: 
 
Table 73: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule with HAI Seroconversion Against 
Seasonal IIV4 Strains at 180 Days Post IIV4 Vaccination, Per Protocol Population  
Table 74: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule with Neut Seroconversion Against 
Seasonal IIV4 Strains at 21 Days Post IIV4 Vaccination, Per Protocol Population*  
Table 75: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule with Neut Seroconversion Against 
Seasonal IIV4 Strains at 180 Days Post IIV4 Vaccination, Per Protocol Population 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 92 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 76: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule with HAI Seroconversion Against 2017 
A/H7N9 at 21 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Adjusted for Baseline Covariates, Per Protocol 
Population* 
Model Parameter 
Parameter Category 
Parameter Estimate 
SE 
p-value 
Odds Ratio 
95%CI 
Intercept 
N/A 
xxx.x 
xxx.x 
x.xxx 
- 
- 
Treatment 
Simultaneous Administration 
(reference) 
- 
- 
- 
- 
- 
 
Sequential Administration 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Age (years) 
N/A 
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 
<30 (reference) 
- 
- 
- 
- 
- 
 
≥30 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Prior 
Receipt 
of 
Influenza Vaccine 
Did Not Receive 2016-2017 
Seasonal Influenza Vaccine 
(reference) 
- 
- 
- 
- 
- 
 
Received 2016-2017 Seasonal 
Influenza Vaccine 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
N = XX (number of subjects in the Per Protocol Population) 
n= XX (number of subjects with results available at 21 days post second dose of AS03 adjuvanted A/H7N9 IIV in the per protocol population.)  
XX subjects missing covariate data were excluded from this analysis. 
 
 
 


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Tables with similar format: 
Table 77: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule with HAI Seroconversion Against 2017 
A/H7N9 at 180 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Adjusted for Baseline Covariates, Per Protocol 
Population 
Table 78: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule with Neut Seroconversion Against 2017 
A/H7N9 at 21 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Adjusted for Baseline Covariates, Per Protocol 
Population*  
Table 79: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule with Neut Seroconversion Against 2017 
A/H7N9 at 180 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Adjusted for Baseline Covariates, Per Protocol 
Population 


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Table 80: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule with HAI Seroconversion Against 
Seasonal IIV4 Strains at 21 Days Post IIV4 Vaccination, Adjusted for Baseline Covariates, Per Protocol Population* 
Model Parameter 
Parameter Category 
Parameter Estimate 
SE 
p-value 
Odds Ratio 
95%CI 
A/Michigan/45/2015 X-275 (H1N1) 
Intercept 
N/A 
xxx.x 
xxx.x 
x.xxx 
- 
- 
Treatment 
Simultaneous 
Administration 
(reference) 
- 
- 
- 
- 
- 
 
Sequential 
Administration 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 
IIV4 Only 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Age (years) 
N/A 
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 
<30 (reference) 
- 
- 
- 
- 
- 
 
≥30 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Prior Receipt of Influenza 
Vaccine  
Did Not Receive 2016-
2017 Seasonal Influenza 
Vaccine (reference) 
- 
- 
- 
- 
- 
 
Received 2016-2017 
Seasonal Influenza 
Vaccine 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
[Repeat for all IIV4 Strains] 
N = XX (Number of subjects in the Per Protocol Population) 
n = XX (number of subjects with results available at 21 days post IIV4 vaccination in the per protocol population).  
XX subjects missing covariate data were excluded from this analysis. 
 
 
 


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Tables with similar format: 
Table 81: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule with HAI Seroconversion Against 
Seasonal IIV4 Strains at 180 Days Post IIV4 Vaccination, Adjusted for Baseline Covariates, Per Protocol Population  
Table 82: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule with Neut Seroconversion Against 
Seasonal IIV4 Strains at 21 Days Post IIV4 Vaccination, Adjusted for Baseline Covariates, Per Protocol Population*  
Table 83: 
Logistic Regression Model to Evaluate the Relationship of Administration Schedule with Neut Seroconversion Against 
Seasonal IIV4 Strains at 180 Days Post IIV4 Vaccination, Adjusted for Baseline Covariates, Per Protocol Population 
 


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Table 84: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration Schedule with Log-Adjusted HAI Titer 
against 2017 A/H7N9 at 21 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per Protocol Population* 
Model Parameter 
Parameter Category 
Parameter Estimate 
SE 
95%CI 
p-value 
Intercept 
N/A 
xxx.x 
xxx.x 
- 
x.xxx 
Treatment 
Simultaneous 
Administration (reference) 
- 
- 
- 
- 
 
Sequential Administration 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
N = XX (Number of subjects in the Per Protocol Population) 
n = XX (number of subjects with results available at 21 days post second dose of AS03 adjuvanted A/H7N9 IIV in the per protocol population.) 
XX subjects missing covariate data were excluded from this analysis. 
 
Tables with similar format: 
 
Table 85: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration Schedule with Log-Adjusted HAI Titer 
against 2017 A/H7N9 at 180 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per Protocol Population  
Table 86: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration Schedule with Log-Adjusted Neut Titer 
against 2017 A/H7N9 at 21 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per Protocol Population*  
Table 87: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration Schedule with Log-Adjusted Neut Titer 
against 2017 A/H7N9 at 180 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Per Protocol Population 
 


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Table 88: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration Schedule with Log-Adjusted HAI Titer 
against Seasonal IIV4 Strains at 21 Days Post IIV4 Vaccination, Per Protocol Population* 
Model Parameter 
Parameter Category 
Parameter Estimate 
SE 
95%CI 
p-value 
A/Michigan/45/2015 X-275 (H1N1) 
Intercept 
N/A 
xxx.x 
xxx.x 
- 
x.xxx 
Treatment 
Simultaneous 
Administration (reference) 
- 
- 
- 
- 
 
Sequential Administration 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 
IIV4 Only 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
[Repeat for all IIV4 Strains] 
N = XX (Number of subjects in the Per Protocol Population) 
n = XX (number of subjects with results available at 21 days post IIV4 vaccination in the per protocol population).  
XX subjects missing covariate data were excluded from this analysis. 
 
Tables with similar format: 
 
Table 89: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration Schedule with Log-Adjusted HAI Titer 
against Seasonal IIV4 Strains at 180 Days Post IIV4 Vaccination, Per Protocol Population  
Table 90: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration Schedule with Log-Adjusted Neut Titer 
against Seasonal IIV4 Strains at 21 Days Post IIV4 Vaccination, Per Protocol Population*  
Table 91: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration Schedule with Log-Adjusted Neut Titer 
against Seasonal IIV4 Strains at 180 Days Post IIV4 Vaccination, Per Protocol Population 
 
 


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Table 92: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration Schedule with Log-Adjusted HAI Titer 
against 2017 A/H7N9 at 21 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Adjusted for Baseline Covariates, 
Per Protocol Population* 
Model Parameter 
Parameter Category 
Parameter Estimate 
SE 
95%CI 
p-value 
Intercept 
N/A 
xxx.x 
xxx.x 
- 
x.xxx 
Treatment 
Simultaneous 
Administration (reference) 
- 
- 
- 
- 
 
Sequential Administration 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Age (years) 
N/A 
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 
<30 (reference) 
- 
- 
- 
- 
 
≥30 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Prior Receipt of Influenza 
Vaccine  
Did Not Receive 2016-2017 
Seasonal Influenza Vaccine 
(reference) 
- 
- 
- 
- 
 
Received 2016-2017 
Seasonal Influenza Vaccine 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
N = XX (Number of subjects in the Per Protocol Population) 
n = XX (number of subjects with results available at 21 days post IIV4 vaccination in the per protocol population).  
XX subjects missing covariate data were excluded from this analysis. 
Tables with similar format: 
 
Table 93: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration Schedule with Log-Adjusted HAI Titer at 
180 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Adjusted for Baseline Covariates, Per Protocol Population  
Table 94: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration Schedule with Log-Adjusted Neut Titer at 
21 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Adjusted for Baseline Covariates, Per Protocol Population*   
Table 95: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration Schedule with Log-Adjusted Neut Titer at 
180 Days Post Second Dose of AS03 adjuvanted A/H7N9 Vaccine, Adjusted for Baseline Covariates, Per Protocol Population  
 


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Table 96: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration Schedule with Log-Adjusted HAI Titer 
against Seasonal IIV4 Strains at 21 Days Post IIV4 Vaccination, Adjusted for Baseline Covariates, Per Protocol Population* 
Model Parameter 
 
Parameter Estimate 
SE 
95%CI 
p-value 
A/Michigan/45/2015 X-275 (H1N1) 
Intercept 
N/A 
xxx.x 
xxx.x 
- 
x.xxx 
Treatment 
Simultaneous 
Administration (reference) 
- 
- 
- 
- 
 
Sequential Administration 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 
IIV4 Only 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Age (years) 
N/A 
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 
<30 (reference) 
- 
- 
- 
- 
 
≥30 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Prior Receipt of Influenza 
Vaccine  
Did Not Receive 2016-2017 
Seasonal Influenza Vaccine 
(reference) 
- 
- 
- 
- 
 
Received 2016-2017 
Seasonal Influenza Vaccine 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
[Repeat for all IIV4 Strains] 
N = XX (Number of subjects in the Per Protocol Population) 
n = XX (number of subjects with results available at 21 days post IIV4 vaccination in the per protocol population).  
XX subjects missing covariate data were excluded from this analysis. 
 
 
 


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Tables with similar format: 
 
Table 97: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration Schedule with Log-Adjusted HAI Titer 
against Seasonal IIV4 Strains at 180 Days Post IIV4 Vaccination, Adjusted for Baseline Covariates, Per Protocol Population  
Table 98: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration Schedule with Log-Adjusted Neut Titer 
against Seasonal IIV4 Strains at 21 Days Post IIV4 Vaccination, Adjusted for Baseline Covariates, Per Protocol Population   
Table 99: 
Multiple Linear Regression Model to Evaluate the Relationship of Administration Schedule with Log-Adjusted Neut Titer 
against Seasonal IIV4 Strains at 180 Days Post IIV4 Vaccination, Adjusted for Baseline Covariates, Per Protocol Population  
 


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14.3 
Safety Data 
14.3.1 Displays of Adverse Events 
Table 100: Overall Summary of Adverse Events, Safety Population* 
 
Group 1: 
Simultaneous 
Administration 
(N=X) 
Group 2: 
Sequential 
Administration  
(N=X) 
Group 3: 
IIV4 Only 
(N=X) 
Subjectsa with 
n 
% 
n 
% 
n 
% 
 
 
 
 
 
 
 
At least one local solicited adverse event 
x 
x 
x 
x 
x 
x 
At least one systemic solicited adverse event 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
At least one unsolicited adverse event 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
At least one related unsolicited adverse event 
x 
x 
x 
x 
x 
x 
     Mild (Grade 1) 
x 
x 
x 
x 
x 
x 
     Moderate (Grade 2)  
x 
x 
x 
x 
x 
x 
     Severe (Grade 3)  
x 
x 
x 
x 
x 
x 
     Not yet assessed 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one severe (Grade 3) unsolicited adverse event 
x 
x 
x 
x 
x 
x 
     Related  
x 
x 
x 
x 
x 
x 
     Unrelated 
x 
x 
x 
x 
x 
x 
     Not yet assessed 
 
 
 
 
 
 
 
 
 
 
 
 
 
At least one serious adverse eventb 
x 
x 
x 
x 
x 
x 
At least one related, serious adverse event 
x 
x 
x 
x 
x 
x 


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Table 100: Overall Summary of Adverse Events, Safety Population (continued) 
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Group 1: 
Simultaneous 
Administration 
(N=X) 
Group 2: 
Sequential 
Administration  
(N=X) 
Group 3: 
IIV4 Only 
(N=X) 
Subjectsa with 
n 
% 
n 
% 
n 
% 
At least one adverse event leading to early terminationc  
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
At least one medically attended adverse event 
x 
x 
x 
x 
x 
x 
At least one new onset chronic medical condition 
x 
x 
x 
x 
x 
x 
At least one potentially immune mediated medical condition 
x 
x 
x 
x 
x 
x 
N = Number of subjects in the safety population. 
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 126 
c As reported on the Adverse Event eCRF 
 


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Table 101: Number of Adverse Events Occurring in 5% of Subjects in Any Treatment Group by MedDRA® System Organ Class and 
Preferred Term, and Treatment Group - Safety Population 
MedDRA System Organ Class 
Preferred Term 
Group 1: 
Simultaneous 
Administration 
(N=X) 
Group 2: 
Sequential Administration  
(N=X) 
Group 3: 
IIV4 Only 
(N=X) 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
Serious Adverse Events 
All 
All  
x 
x 
x 
x 
x 
x 
x 
x 
x 
SOC1 
PT1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Etc. 
Etc. 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Other (Non-serious) Adverse Events 
All 
All  
x 
x 
x 
x 
x 
x 
x 
x 
x 
SOC1 
PT1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Etc 
Etc 
x 
x 
x 
x 
x 
x 
x 
x 
x 
N = number of subjects in the safety population. n= number of subjects reporting event. Events = total frequency of events reported. 
MedDRA Version X.X. 
 
 


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14.3.1.1 
Solicited Adverse Events 
Table 102: Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom and 
Treatment Group (Safety Population) – Post Any Study Dose* 
Symptom 
Group 1: 
Simultaneous Administration 
(N=X) 
Group 2: 
Sequential Administration  
(N=X) 
Group 3: 
IIV4 Only 
(N=X) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
Any Symptom 
x 
xx  
(xx-xx) 
x 
xx  
(xx-xx) 
x 
xx  
(xx-xx) 
Any Systemic Symptom 
 
 
 
 
 
 
Fever 
 
 
 
 
 
 
Feverishness 
 
 
 
 
 
 
Fatigue 
 
 
 
 
 
 
Malaise 
 
 
 
 
 
 
Myalgia 
 
 
 
 
 
 
Arthralgia 
 
 
 
 
 
 
Headache 
 
 
 
 
 
 
Nausea 
 
 
 
 
 
 
Any Local Symptom 
 
 
 
 
 
 
Pain 
 
 
 
 
 
 
Tenderness 
 
 
 
 
 
 
Pruritus 
 
 
 
 
 
 
Ecchymosis 
 
 
 
 
 
 
Ecchymosis (measurement) 
 
 
 
 
 
 
Erythema 
 
 
 
 
 
 
Erythema (measurement) 
 
 
 
 
 
 
Induration/Swelling 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
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Table 102: Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom and 
Treatment Group (Safety Population) – Post Any Study Dose (continued) 
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Symptom 
Group 1: 
Simultaneous Administration 
(N=X) 
Group 2: 
Sequential Administration  
(N=X) 
Group 3: 
IIV4 Only 
(N=X) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
Induration/Swelling (measurement) 
 
 
 
 
 
 
N = Number of subjects in the Safety Population who received any dose. 
95% CI estimated using Clopper-Pearson exact method 
 
Tables with similar format: 
Table 103: Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom and 
Treatment Group (Safety Population) – Post Study Dose 1* 
[Footnote update] N = Number of subjects in the Safety Population who received the first dose. 
 
Table 104: Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom and 
Treatment Group (Safety Population) – Post Study Dose 2* 
[Footnote update] N = Number of subjects in the Safety Population who received the second dose. 
 
Table 105: Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom and 
Treatment Group (Safety Population) – Post Study Dose 3* 
[Footnote update] N = Number of subjects in the Safety Population who received the third dose. 
 


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Table 106: Logistic Regression Model to Evaluate the Relationship of Treatment with Reporting Any Local Event Post Any Study Dose 
(Safety Population) * 
Model Parameter 
Parameter Category 
Parameter Estimate 
SE 
p-value 
Odds Ratio 
95%CI 
Intercept 
N/A 
xxx.x 
xxx.x 
x.xxx 
- 
- 
Treatment 
 Simultaneous 
Administration 
(reference) 
- 
- 
- 
- 
- 
 
 Sequential 
Administration 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 
 IIV4 Only 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
N = number of subjects in the safety population. 
 
Table with similar format: 
 
Table 107: Logistic Regression Model to Evaluate the Relationship of Treatment with Reporting Any Systemic Event Post Any Study 
Dose (Safety Population) * 
 


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Table 108: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity and 
Treatment Group (Safety Population) – Post Any Study Dose* 
Symptom 
Severity 
Group 1: 
Simultaneous Administration 
(N=X) 
Group 2: 
Sequential Administration  
(N=X) 
Group 3: 
IIV4 Only 
(N=X) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
Any Symptom 
None 
x 
xx (xx-xx) 
x 
xx (xx-xx) 
x 
xx (xx-xx) 
 
Mild 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
Any Systemic Symptom 
None 
x 
xx (xx-xx) 
x 
xx (xx-xx) 
x 
xx (xx-xx) 
 
Mild 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
Fever 
None 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
Feverishness 
None 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
Fatigue 
None 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
Malaise 
None 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
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Table 108: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity and Treatment Arm 
(Safety Population)  – Post Any Study Dose (continued) 
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Symptom 
Severity 
Group 1: 
Simultaneous Administration 
(N=X) 
Group 2: 
Sequential Administration  
(N=X) 
Group 3: 
IIV4 Only 
(N=X) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
 
Moderate 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
Myalgia 
None 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
Arthralgia 
None 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
Headache 
None 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
Nausea 
None 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
Any Local Symptom 
None 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
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Table 108: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity and Treatment Arm 
(Safety Population)  – Post Any Study Dose (continued) 
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Symptom 
Severity 
Group 1: 
Simultaneous Administration 
(N=X) 
Group 2: 
Sequential Administration  
(N=X) 
Group 3: 
IIV4 Only 
(N=X) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
Pain 
None 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
Tenderness 
None 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
Pruritus 
None 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
Ecchymosis 
None 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
Ecchymosis (measurement) 
None 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
Erythema 
None 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
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Table 108: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity and Treatment Arm 
(Safety Population)  – Post Any Study Dose (continued) 
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Symptom 
Severity 
Group 1: 
Simultaneous Administration 
(N=X) 
Group 2: 
Sequential Administration  
(N=X) 
Group 3: 
IIV4 Only 
(N=X) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
 
Moderate 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
Erythema (measurement) 
None 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
Induration/Swelling 
None 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
Induration/Swelling 
(measurement) 
None 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
N = Number of subjects in the Safety Population who received any study dose. 
95% CI estimated using Clopper-Pearson exact method 
Severity is the maximum severity reported over all solicited symptoms post dosing for each subject.   


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Tables with similar format: 
Table 109: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity and Treatment Group 
(Safety Population) – Post Study Dose 1* 
[Footnote Update] N = Number of subjects in the Safety Analysis Population who received the first study dose. 
 
Table 110: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity and Treatment Group 
(Safety Population) – Post Study Dose 2* 
[Footnote Update] N = Number of subjects in the Safety Analysis Population who received the second study dose. 
 
Table 111: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity and Treatment Group 
(Safety Population) – Post Study Dose 3* 
[Footnote Update] N = Number of subjects in the Safety Analysis Population who received the third study dose. 
 
 


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Table 112: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Severity, Day Post Dose, and Treatment 
Group (Safety Population) – Post Any Study Dose 
Symptom 
Severity 
Pre-Dose 
Post-
Dose 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Day 8+ 
 
 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Group 1: Simultaneous Administration  (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 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Malaise 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
Table 112: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Severity, Day Post Study Vaccination, and 
Treatment Arm (Safety Population) – Post Any Study Dose (continued) 
- 113 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
Severity 
Pre-Dose 
Post-
Dose 
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 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Myalgia 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Arthralgia 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Headache 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nausea 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Any Local Symptom 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pain 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
Table 112: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Severity, Day Post Study Vaccination, and 
Treatment Arm (Safety Population) – Post Any Study Dose (continued) 
- 114 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
Severity 
Pre-Dose 
Post-
Dose 
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 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
Table 112: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Severity, Day Post Study Vaccination, and 
Treatment Arm (Safety Population) – Post Any Study Dose (continued) 
- 115 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Symptom 
Severity 
Pre-Dose 
Post-
Dose 
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 
% 
Erythema (measurement) 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Induration/Swelling 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Induration/Swelling (measurement) 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[repeat for all treatment groups] 
N = Number of subjects in the Safety Analysis Population who received the specified dose. Severity is the maximum severity reported post dosing for each subject for each day. 
Tables with similar format: 
Table 113: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Severity, Day Post Dose, and Treatment 
Group (Safety Population) – Post Study Dose 1 
Table 114: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Severity, Day Post Dose, and Treatment 
Group (Safety Population) – Post Study Dose 2 
Table 115: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Severity, Day Post Dose, and Treatment 
Group (Safety Population) – Post Study Dose 3 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 116 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 116: Comparison of the Number and Percentage of Subjects Experiencing Solicited Systemic Events by Dose and Treatment 
Group – Safety Population 
 
 
Subjects with No 
Symptoms 
Subjects with Mild or Greater 
Symptoms 
Total Number of Subjects 
n (Percent) 
[p-value*] 
Study Dose 1 vs Study Dose 2 
Group 1: 
Simultaneous 
Administration 
(N=X) 
Subjects with No Symptoms  
x (%) 
x (%) 
x (%) 
Subjects with Mild or Greater 
Symptoms  
x (%) 
x (%) 
x (%) 
Total Number of Subjects  
x (%) 
x (%) 
x (100%) 
[0.xxx] 
Group 2: 
Sequential 
Administration 
(N=X) 
Subjects with No Symptoms  
x (%) 
x (%) 
x (%) 
Subjects with Mild or Greater 
Symptoms  
x (%) 
x (%) 
x (%) 
Total Number of Subjects  
x (%) 
x (%) 
x (100%) 
[0.xxx] 
Study Dose 1 vs Study Dose 3 
Group 2: 
Sequential 
Administration 
(N=X) 
Subjects with No Symptoms  
x (%) 
x (%) 
x (%) 
Subjects with Mild or Greater 
Symptoms  
x (%) 
x (%) 
x (%) 
Total Number of Subjects  
x (%) 
x (%) 
x (100%) 
[0.xxx] 
Study Dose 2 vs Study Dose 3 
Group 2: 
Sequential 
Administration 
(N=X) 
Subjects with No Symptoms  
x (%) 
x (%) 
x (%) 
Subjects with Mild or Greater 
Symptoms  
x (%) 
x (%) 
x (%) 
Total Number of Subjects  
x (%) 
x (%) 
x (100%) 
[0.xxx] 
Note: Denominators for percentages are the number of subjects in the safety population who received both the first and second study dose. Subjects who did 
not receive both indicated doses are not included in this table. [x] subjects did not receive the second dose and [x] subjects did not receive the third dose.  
* P-value is calculated from McNemar's test for each treatment group. 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
 
- 117 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table with similar format: 
Table 117: Comparison of the Number and Percentage of Subjects Experiencing Solicited Local Events by Dose and Treatment Group  – 
Safety Population 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
- 118 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.3.1.2 
Unsolicited Adverse Events 
Table 118: Number and Percentage of Subjects Experiencing Unsolicited Adverse Events with 95% Confidence Intervals by 
MedDRA® System Organ Class and Preferred Term, and Treatment Group – Safety Population* 
MedDRA® System Organ 
Class 
MedDRA® Preferred 
Term 
Group 1: 
Simultaneous Administration 
(N=X) 
Group 2: 
Sequential Administration  
(N=X) 
Group 3: 
IIV4 Only 
(N=X) 
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) 
[SOC 1] 
Any PT 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
Note: N = number of subjects in the Safety Analysis Population who received any dose. This table presents number and percentage of subjects. A subject is only counted once 
per PT. 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 119 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 119: Number and Percentage of Subjects Experiencing Unsolicited Adverse Events by MedDRA® System Organ Class and 
Preferred Term, Maximum Severity, Relationship, and Treatment Group – Safety Population* 
Treatment Group 
MedDRA® System 
Organ Class 
MedDRA® Preferred 
Term 
Any Incide
nce 
Severity [1] 
Relationship to Treatment [2] 
Mild 
Moderate 
Severe 
Not Related 
Related 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Group 1: 
Simultaneous 
Administration  
(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] 
 
 
 
 
 
 
 
 
 
 
 
 
Group 2: Sequential 
Administration  
(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] 
 
 
 
 
 
 
 
 
 
 
 
 
Group 3: IIV4 Only 
(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] 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
Table 119: Number and Percentage of Subjects Experiencing Unsolicited Adverse Events by MedDRA® System Organ Class and 
Preferred Term, Maximum Severity, Relationship, and Treatment Group – Safety Population (continued) 
- 120 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Treatment Group 
MedDRA® System 
Organ Class 
MedDRA® Preferred 
Term 
Any Incide
nce 
Severity [1] 
Relationship to Treatment [2] 
Mild 
Moderate 
Severe 
Not Related 
Related 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N = Number of subjects in the Safety Analysis Population.  
[1] For severity, a subject is counted once per preferred term and is summarized according to their highest severity. 
[2] For relationship, a subject is only counted once per preferred term and is summarized according to their closest relationship. 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 121 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 120: Number and Percentage of Subjects Experiencing Non-Serious Related Unsolicited Adverse Events by MedDRA® System 
Organ Class and Preferred Term, Maximum Severity, and Treatment Group – Safety Population 
Treatment Group 
MedDRA® System Organ 
Class 
MedDRA® Preferred 
Term 
Any Incidence 
Severity [1] 
Mild 
Moderate 
Severe 
n 
% 
n 
% 
n 
% 
n 
% 
Group 1: Simultaneous 
Administration  
(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] 
 
 
 
 
 
 
 
 
Group 2: Sequential 
Administration  
(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] 
 
 
 
 
 
 
 
 
Group 3: IIV4 Only 
(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 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
Table 120: Number and Percentage of Subjects Experiencing Non-Serious Related Unsolicited Adverse Events by MedDRA® System 
Organ Class and Preferred Term, Maximum Severity, and Treatment Group – Safety Population (continued) 
- 122 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Treatment Group 
MedDRA® System Organ 
Class 
MedDRA® Preferred 
Term 
Any Incidence 
Severity [1] 
Mild 
Moderate 
Severe 
n 
% 
n 
% 
n 
% 
n 
% 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
Note: N = Number of subjects in the Safety Analysis Population. This table presents number and percentage of subjects.  
[1] For severity, a subject is counted once per preferred term and is summarized according to their highest severity. 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 123 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 121: Number and Percentage of Subjects Experiencing Unsolicited Adverse Events Within 21 Days Post Dose by MedDRA® 
System Organ Class and Preferred Term, Day Post Dose, and Treatment Group – Safety Population 
MedDRA® 
System Organ 
Class 
MedDRA® 
Preferred Term 
Day 1-8 
Post 
Dose 1 
Day 9-
22 
Post 
Dose 1 
Day 1-
22 
Post 
Dose 1 
Day 1-8 
Post Dose 
2 
Day 9-22 
Post Dose 
2 
Day 1-22 
Post Dose 
2 
Day 1-8 
Post 
Dose 3 
Day 1-8 
Post 
Dose 3 
Day 1-8 
Post 
Dose 3 
Day 1-22 
Post Any 
Dose 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Group 1: Simultaneous Administration  (N=X) 
Any SOC 
Any PT 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
NA 
NA 
NA 
NA 
NA 
NA 
x 
xx 
[SOC 1] 
Any PT 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
NA 
NA 
NA 
NA 
NA 
NA 
x 
xx 
 
[PT 1] 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
NA 
NA 
NA 
NA 
NA 
NA 
x 
xx 
 
[PT 2] 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
NA 
NA 
NA 
NA 
NA 
NA 
x 
xx 
[SOC 2] 
Any PT 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
NA 
NA 
NA 
NA 
NA 
NA 
x 
xx 
 
[PT 1] 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
NA 
NA 
NA 
NA 
NA 
NA 
x 
xx 
 
[PT 2] 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
NA 
NA 
NA 
NA 
NA 
NA 
x 
xx 
Group 2: Sequential Administration (N=X) 
Any SOC 
Any PT 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
[SOC 1] 
Any PT 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
[PT 1] 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
[PT 2] 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
[SOC 2] 
Any PT 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
[PT 1] 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
[PT 2] 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Group 3: IIV4 Only (N=X) 
Any SOC 
Any PT 
x 
xx 
x 
xx 
x 
xx 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
x 
xx 
[SOC 1] 
Any PT 
x 
xx 
x 
xx 
x 
xx 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
x 
xx 
 
[PT 1] 
x 
xx 
x 
xx 
x 
xx 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
x 
xx 
 
[PT 2] 
x 
xx 
x 
xx 
x 
xx 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
x 
xx 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
Table 121: Number and Percentage of Subjects Experiencing Unsolicited Adverse Events Within 21 Days Post Dose by MedDRA® 
System Organ Class and Preferred Term, Day Post Dose, and Treatment Group – Safety Population (continued) 
- 124 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
MedDRA® 
System Organ 
Class 
MedDRA® 
Preferred Term 
Day 1-8 
Post 
Dose 1 
Day 9-
22 
Post 
Dose 1 
Day 1-
22 
Post 
Dose 1 
Day 1-8 
Post Dose 
2 
Day 9-22 
Post Dose 
2 
Day 1-22 
Post Dose 
2 
Day 1-8 
Post 
Dose 3 
Day 1-8 
Post 
Dose 3 
Day 1-8 
Post 
Dose 3 
Day 1-22 
Post Any 
Dose 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
[SOC 2] 
Any PT 
x 
xx 
x 
xx 
x 
xx 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
x 
xx 
 
[PT 1] 
x 
xx 
x 
xx 
x 
xx 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
x 
xx 
 
[PT 2] 
x 
xx 
x 
xx 
x 
xx 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
x 
xx 
Note: N = Number of subjects in the Safety Analysis Population. This table presents number and percentage of subjects. For each time period, a subject is only counted once per 
PT. 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 125 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 122: Number and Percentage of Subjects Experiencing Non-Serious, Related Unsolicited Adverse Events Within 21 Days Post Dose 
by MedDRA® System Organ Class and Preferred Term, Dose and Treatment Group – Safety Population 
 
 
Day 1-8 
Post 
Dose 1 
Day 9-
22 
Post 
Dose 1 
Day 1-
22 
Post 
Dose 1 
Day 1-8 
Post Dose 
2 
Day 9-22 
Post Dose 
2 
Day 1-22 
Post Dose 
2 
Day 1-8 
Post 
Dose 3 
Day 1-8 
Post 
Dose 3 
Day 1-8 
Post 
Dose 3 
Day 1-22 
Post Any 
Dose 
MedDRA® 
System Organ 
Class 
MedDRA® 
Preferred Term 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Group 1: Simultaneous Administration   (N=X) 
Any SOC 
Any PT 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
NA 
NA 
NA 
NA 
NA 
NA 
x 
xx 
[SOC 1] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Group 2: Sequential Administration (N=X) 
Any SOC 
Any PT 
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] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Group 3: IIV4 Only (N=X) 
Any SOC 
Any PT 
x 
xx 
x 
xx 
x 
xx 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
x 
xx 
[SOC 1] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
Table 122: Number and Percentage of Subjects Experiencing Non-Serious, Related Unsolicited Adverse Events Within 21 Days Post Dose 
by MedDRA® System Organ Class and Preferred Term, Dose and Treatment Group – Safety Population (continued) 
- 126 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
 
 
Day 1-8 
Post 
Dose 1 
Day 9-
22 
Post 
Dose 1 
Day 1-
22 
Post 
Dose 1 
Day 1-8 
Post Dose 
2 
Day 9-22 
Post Dose 
2 
Day 1-22 
Post Dose 
2 
Day 1-8 
Post 
Dose 3 
Day 1-8 
Post 
Dose 3 
Day 1-8 
Post 
Dose 3 
Day 1-22 
Post Any 
Dose 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N = Number of subjects in the Safety Analysis Population. This table presents number and percentage of subjects. For each time period, a subject is only counted once 
per PT. 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 127 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 123: Number of Unsolicited Adverse Events by MedDRA® System Organ Class and Preferred Term, Day Post Dose, and 
Treatment Group – Safety Population 
 
 
 
Day 1-
8 
Post 
Dose 1 
Day 9-
22 
Post 
Dose  1 
Day 1-
22 
Post 
Dose 1 
Day 1-
8 
Post 
Dose 2 
Day 9-
22 
Post 
Dose 2 
Day 1-
22 
Post 
Dose 2 
Day 1-
8 
Post 
Dose 3 
Day 9-
22 
Post 
Dose  3 
Day 1-
22 
Post 
Dose 3 
Day 1-
22 
Post 
Any 
Dose 
Treatment 
Group 
MedDRA® System 
Organ Class 
MedDRA® 
Preferred Term 
# of 
Events 
# of 
Events 
# of 
Events 
# of 
Events 
# of 
Events 
# of 
Events 
# of 
Events 
# of 
Events 
# of 
Events 
# of 
Events 
Group 1: 
Simultaneous 
Administration  
(N=X) 
Any SOC 
Any PT 
x 
x 
x 
x 
x 
x 
NA 
NA 
NA 
x 
 
[SOC 1] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
Group 2: 
Sequential 
Administration 
(N=X) 
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] 
 
 
 
 
 
 
 
 
 
 
Group 3:  
IIV4 Only 
(N=X) 
Any SOC 
Any PT 
x 
x 
x 
NA 
NA 
NA 
NA 
NA 
NA 
x 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
Table 123: Number of Unsolicited Adverse Events by MedDRA® System Organ Class and Preferred Term, Day Post Dose, and 
Treatment Group – Safety Population (continued) 
- 128 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
 
 
 
Day 1-
8 
Post 
Dose 1 
Day 9-
22 
Post 
Dose  1 
Day 1-
22 
Post 
Dose 1 
Day 1-
8 
Post 
Dose 2 
Day 9-
22 
Post 
Dose 2 
Day 1-
22 
Post 
Dose 2 
Day 1-
8 
Post 
Dose 3 
Day 9-
22 
Post 
Dose  3 
Day 1-
22 
Post 
Dose 3 
Day 1-
22 
Post 
Any 
Dose 
 
[SOC 1] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
Note: N = Number of subjects in the Safety Analysis Population. This table presents number of events; a subject may be counted multiple times. 
 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
- 129 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.3.2 Listings of Serious and Significant Adverse Events 
Table 124: Listing of Serious Adverse Events * 
[Implementation Note: If the event is ongoing (no stop date), indicate “ongoing” in the “Duration” column. If more than one reason is selected for 
the reason reported as an SAE, list all reasons in the column, separated by a comma.In the “If Not Related, Alternate Etiology” column, merge the 
2 data fields for collecting alternate etiology, separate by a colon.In the CSR, Subject ID should be USUBJID (not PATID) for purposes of de-
identification.] 
Adverse 
Event 
Associated 
with Dose 
# 
# of Days 
Post 
Associated 
Dose 
(Duration) 
# of 
Days 
Post 
Dose the 
Event 
Became 
Serious 
Reason 
Reported 
as an SAE 
Severity 
Relationship 
to Study 
Treatment 
In Not 
Related, 
Alternative 
Etiology 
Action 
Taken with 
Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
MedDRA® 
Sytem 
Organ 
Class 
MedDRA® 
Preferred 
Term 
Subject ID: , Treatment Group: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 
Subject ID: , Treatment Group: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
- 130 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 125: Listing of Medically Attended Adverse Events* 
[Implementation Note: If the event is ongoing (no stop date), indicate “ongoing” in the “Duration” column. In the “If Not Related, Alternate Etiology” 
column, merge the 2 data fields for collecting alternate etiology, separate by a colon.] 
Adverse 
Event 
Associated 
with Dose 
# 
# of Days 
Post 
Associated 
Dose 
(Duration) 
SAE? 
Severity 
Relationship 
to Study 
Treatment 
In Not 
Related, 
Alternative 
Etiology 
Action 
Taken 
with 
Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
MAAE 
MedDRA® 
System 
Organ 
Class 
MedDRA® 
Preferred 
Term 
Subject ID: , Treatment Group: , AE Number:  
 
 
 
SAE: No 
Mild 
 
 
 
 
 
 
 
 
Comments: 
 
 
Subject ID: , Treatment Group: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 
Tables with similar format: 
Table 126: Listing of Potentially Immune Mediated Medical Conditions* 
Table 127: Listing of New Onset Chronic Medical Conditions* 
Table 128: Listing of Non-Serious, Unsolicited, Moderate or Severe Adverse Events* 
 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
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PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.3.3 Narratives of Deaths, Other Serious and Significant Adverse Events  
(not included in SAP, placeholder for the CSR) 
 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
 
14 November 2018 
- 132 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.3.4 Displays of Laboratory Results 
Table 129: Laboratory Results by Parameter, Maximum Severity, Study Day, and Treatment Group (Safety Population)  – 
All Laboratory Parameters * 
Treatment Group 
Study Day 
N 
None 
Mild/ 
Grade 1 
Moderate/ 
Grade 2 
Severe/ 
Grade 3 
Missing 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Group 1: 
Simultaneous 
Administration  
(N=X) 
 
Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 8 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 22 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 29 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 43 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
Day 50 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
Max Severity Post 
Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Group 2: Sequential 
Administration 
(N=X) 
Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 8 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 22 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 29 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 43 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 50 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Max Severity Post 
Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Group 3: IIV4 Only 
(N=X) 
Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 8 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 22 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
Day 29 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
Day 43 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
Day 50 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
Table 129: Laboratory Results by Parameter, Maximum Severity, Study Day, and Treatment Group (Safety Population)  – All 
Laboratory Parameters (continued) 
- 133 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
 
 
 
Max Severity Post 
Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Note: The “Max Post Baseline” rows indicate the maximum severity experienced by each subject at any time point post baseline, including unscheduled 
assessments.  
N=Number of subjects in the Safety population. 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
 
14 November 2018 
- 134 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 130: Laboratory Results by Parameter, Maximum Severity, Study Day, and Treatment Group (Safety Population)  – White Blood 
Cells* 
Treatment Group 
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 
% 
Group 1: Simultaneous 
Administration  (N=X) 
Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 8 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 22 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 29 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 43 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
Day 50 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
Max Severity 
Post Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Group 2: Sequential 
Administration (N=X) 
Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 8 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 22 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 29 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 43 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 50 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Max Severity 
Post Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Group 3: IIV4 Only 
(N=X) 
Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 8 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 22 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
Day 29 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
Day 43 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 


Statistical Analysis Plan - DMID Protocol: 17-0077 
Version 1.0 
14 November 2018 
Table 130: Laboratory Results by Parameter, Maximum Severity, Study Day, and Treatment Group (Safety Population)  – White Blood 
Cells (continued) 
- 135 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
 
 
Tables with similar format: 
 
Table 131: Laboratory Results by Parameter, Maximum Severity, Study Day, and Treatment Group (Safety Population)  – Hemoglobin* 
Table 132: Laboratory Results by Parameter, Maximum Severity, Study Day, and Treatment Group (Safety Population)  – Platelets* 
Table 133: Laboratory Results by Parameter, Maximum Severity, Study Day, and Treatment Group (Safety Population)  – Alanine 
aminotransferase (ALT) * 
Table 134: Laboratory Results by Parameter, Maximum Severity, Study Day, and Treatment Group (Safety Population)  – Total 
Bilirubin * 
Table 135: Laboratory Results by Parameter, Maximum Severity, Study Day, and Treatment Group (Safety Population)  – Creatinine* 
 
Day 50 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
Max Severity 
Post Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Note: The “Max Post Baseline” rows indicate the maximum severity experienced by each subject at any time point post baseline, including unscheduled 
assessments.  
N=Number of subjects in the Safety population. 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 136 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 136: Laboratory Summary Statistics of Value and Change from Baseline by Study Day, and Treatment Group (Safety Population)  
– White Blood Cells* 
Treatment 
Group 
Study 
Day 
Value 
Change from Baseline 
N 
Mean 
Standard 
Deviation 
Median 
Min, Max 
N 
Mean 
Standard 
Deviation 
Median 
Min, Max 
Group 1: 
Simultaneous 
Administration  
(N=X) 
 
Baseline 
x 
xx.x 
xx.x 
xx 
xx, xx 
NA 
NA 
NA 
NA 
NA 
Day 8 
x 
xx.x 
xx.x 
xx 
xx, xx 
x 
xx.x 
xx.x 
xx 
xx, xx 
Day 22 
x 
xx.x 
xx.x 
xx 
xx, xx 
x 
xx.x 
xx.x 
xx 
xx, xx 
Day 29 
x 
xx.x 
xx.x 
xx 
xx, xx 
x 
xx.x 
xx.x 
xx 
xx, xx 
Day 43 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
Day 50 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
Group 2: 
Sequential 
Administration 
(N=X) 
 
Baseline 
x 
xx.x 
xx.x 
xx 
xx, xx 
NA 
NA 
NA 
NA 
NA 
Day 8 
x 
xx.x 
xx.x 
xx 
xx, xx 
x 
xx.x 
xx.x 
xx 
xx, xx 
Day 22 
x 
xx.x 
xx.x 
xx 
xx, xx 
x 
xx.x 
xx.x 
xx 
xx, xx 
Day 29 
x 
xx.x 
xx.x 
xx 
xx, xx 
x 
xx.x 
xx.x 
xx 
xx, xx 
Day 43 
x 
xx.x 
xx.x 
xx 
xx, xx 
x 
xx.x 
xx.x 
xx 
xx, xx 
Day 50 
x 
xx.x 
xx.x 
xx 
xx, xx 
x 
xx.x 
xx.x 
xx 
xx, xx 
Group 3: IIV4 
Only (N=X) 
Baseline 
x 
xx.x 
xx.x 
xx 
xx, xx 
NA 
NA 
NA 
NA 
NA 
Day 8 
x 
xx.x 
xx.x 
xx 
xx, xx 
x 
xx.x 
xx.x 
xx 
xx, xx 
Day 22 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
Day 29 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
Day 43 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
Day 50 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
N= Number of subjects in the Safety population 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 137 - 
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Tables with similar format: 
Table 137: Laboratory Summary Statistics of Value and Change from Baseline by Study Day, and Treatment Group (Safety Population)  
– Hemoglobin* 
Table 138: Laboratory Summary Statistics of Value and Change from Baseline by Study Day, and Treatment Group (Safety Population)  
– Platelets* 
Table 139: Laboratory Summary Statistics of Value and Change from Baseline by Study Day, and Treatment Group (Safety Population)  
– Alanine Aminotransferase* (ALT) 
Table 140: Laboratory Summary Statistics of Value and Change from Baseline by Study Day, and Treatment Group (Safety Population)  
– Total Bilirubin* 
Table 141: Laboratory Summary Statistics of Value and Change from Baseline by Study Day, and Treatment Group (Safety Population)  
– Creatinine* 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 138 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.3.4.5 
Clinical Laboratory Reference Ranges 
(Placeholder for the CSR) 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 139 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.3.5 Abnormal Laboratory Value Listings (by Subject) 
Table 142: Listing of Abnormal Laboratory Results - Chemistry  
Subject 
ID 
Treatment 
Group 
Sex 
Age 
(years) 
Planned 
Time 
Point 
Actual 
Study 
Day 
Laboratory 
Parameter 
(Units) 
Result 
(Severity) 
Relationship 
to Treatment 
If Not 
Related, 
Alternate 
Etiology 
Action 
Taken with 
Study 
Treatment 
Subject 
Discontinued 
Due to 
Result? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 140 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 143: Listing of Abnormal Laboratory Results - Hematology 
Subject 
ID 
Treatment 
Group 
Sex 
Age 
(years) 
Planned 
Time 
Point 
Actual 
Study 
Day 
Laboratory 
Parameter 
(Units) 
Result 
(Severity) 
Relationship 
to Treatment 
If Not 
Related, 
Alternate 
Etiology 
Action 
Taken with 
Study 
Treatment 
Subject 
Discontinued 
Due to 
Result? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 141 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.3.6 Displays of Vital Signs 
Table 144: Vital Signs by Assessment, Maximum Severity, Study Day, Treatment Group (Safety Population)  – Any Assessment* 
Treatment Group 
Study Day 
N 
None 
Mild 
Moderate 
Severe 
Missing 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Group 1: Simultaneous 
Administration  (N=X) 
 
Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Day 22 
 
 
 
 
 
 
 
 
 
 
 
Day 43 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
Max Severity Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
Group 2: Sequential 
Administration (N=X) 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
Day 22 
 
 
 
 
 
 
 
 
 
 
 
Day 43 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
Group 3: IIV4 Only 
(N=X) 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
Day 22 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
Day 43 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
Max Severity Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
Note: The “Max Post Baseline” rows indicate the maximum severity experienced by each subject at any time point post baseline, including unscheduled assessments.  
N= Number of subjects in the Safety population. 
 
Table with similar format: 
Table 145: Vital Signs by Assessment, Maximum Severity, Study Day, Treatment Group (Safety Population)  – Oral Temperature 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 142 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
Table 146: Vital Signs by Assessment, Maximum Severity, Study Day, and Treatment Group (Safety Population)  – Systolic Blood 
Pressure 
Treatment 
Group 
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 
% 
Group 1: 
Simultaneous 
Administration  
(N=X) 
 
Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Day 22 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Day 43 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
 
Max Severity 
Post Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Group 2: 
Sequential 
Administration 
(N=X) 
Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Day 22 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Day 43 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Max Severity 
Post Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Group 3: IIV4 
Only (N=X) 
Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Day 22 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
 
Day 43 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
 
Max Severity 
Post Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Note: The “Max Post Baseline” rows indicate the maximum severity experienced by each subject at any time point post baseline, including unscheduled assessments.  
N=Number of subjects in the Safety population. 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
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Tables with similar format: 
Table 147: Vital Signs by Assessment, Maximum Severity, Study Day, and Treatment Group (Safety Population)  – Diastolic Blood 
Pressure 
Table 148: Vital Signs by Assessment, Maximum Severity, Study Day, and Treatment Group (Safety Population)  – Pulse 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 144 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
14.4 
Summary of Concomitant Medications 
Table 149: Number and Percentage of Subjects with Prior and Concurrent Medications by 
WHO Drug Classification and Treatment Group – Safety Population 
WHO Drug Code 
Level 1, Anatomic Group 
WHO Drug Code 
Level 2, Therapeutic 
Subgroup 
Group 1: 
Simultaneous 
Administration  
(N=X) 
Group 2: 
Sequential 
Administration 
(N=X) 
Group 3:  
IIV4 Only (N=X) 
n 
% 
n 
% 
n 
% 
Any Level 1 Codes 
Any Level 2 Codes 
x 
xx 
x 
xx 
x 
xx 
[ATC Level 1 - 1] 
Any [ATC 1 – 1] 
 
 
 
 
 
 
 
[ATC 2 - 1] 
 
 
 
 
 
 
 
[ATC 2 - 2] 
 
 
 
 
 
 
 
[ATC 2 - 3] 
 
 
 
 
 
 
[ATC Level 1 – 2] 
[ATC 2 - 1] 
 
 
 
 
 
 
 
[ATC 2 - 2] 
 
 
 
 
 
 
 
[ATC 2 - 3] 
 
 
 
 
 
 
N= Number of subjects in the Safety population. n=Number of subjects reporting taking at least one medication in the 
specific WHO Drug Class. 
 


Statistical Analysis Plan - DMID Protocol: 17-0077  
Version 1.0 
14 November 2018 
- 145 - 
PRIVILEGED AND CONFIDENTIAL COMMUNICATION 
 
FIGURE MOCK-UPS 
 
LIST OF FIGURES 
Figure 1: 
CONSORT Flow Diagram* ........................................................................................ 149 
Figure 2: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody 
against 2017 A/H7N9 by Study Day and Treatment Group, Modified Intent to Treat 
Population* ................................................................................................................. 150 
Figure 3: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
2017 A/H7N9 by Study Day and Treatment Group, Per Protocol Population* .......... 150 
Figure 4: 
Reverse Cumulative Distribution of Neutralizing Antibody Against 2017 A/H7N9 by 
Study Day and Treatment Group, Modified Intent to Treat Population* .................... 150 
Figure 5: 
Reverse Cumulative Distribution of Neutralizing Antibody against 2017 A/H7N9 by 
Study Day and Treatment Group, Per Protocol Population* ...................................... 150 
Figure 6: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody 
against A/Michigan/45/2015 X-275(H1N1) by Study Day and Treatment Group, 
Modified Intent to Treat Population* .......................................................................... 150 
Figure 7: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
A/Michigan/45/2015 X-275(H1N1) by Study Day and Treatment Group, Per Protocol 
Population* ................................................................................................................. 150 
Figure 8: 
Reverse Cumulative Distribution of Neutralizing Antibody Against 
A/Michigan/45/2015 X-275(H1N1) by Study Day and Treatment Group, Modified 
Intent to Treat Population* .......................................................................................... 151 
Figure 9: 
Reverse Cumulative Distribution of Neutralizing Antibody against 
A/Michigan/45/2015 X-275(H1N1) by Study Day and Treatment Group, Per Protocol 
Population* ................................................................................................................. 151 
Figure 10: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody 
against A/Hong Kong/4801/2014 X263B (H3N2) by Study Day and Treatment Group, 
Modified Intent to Treat Population* .......................................................................... 151 
Figure 11: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
A/Hong Kong/4801/2014 X263B (H3N2) by Study Day and Treatment Group, Per 
Protocol Population* ................................................................................................... 151 
Figure 12: 
Reverse Cumulative Distribution of Neutralizing Antibody Against A/ Hong 
Kong/4801/2014 X263B (H3N2) by Study Day and Treatment Group, Modified Intent 
to Treat Population* .................................................................................................... 151 
Figure 13: 
Reverse Cumulative Distribution of Neutralizing Antibody against A/ Hong 
Kong/4801/2014 X263B (H3N2) by Study Day and Treatment Group, Per Protocol 
Population* ................................................................................................................. 151 
Figure 14: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody 
against B/Phuket/3073/2013 (B Yamagata lineage) by Study Day and Treatment 
Group, Modified Intent to Treat Population* .............................................................. 151 
Figure 15: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
B/Phuket/3073/2013 (B Yamagata lineage) by Study Day and Treatment Group, Per 
Protocol Population* ................................................................................................... 151 
Figure 16: 
Reverse Cumulative Distribution of Neutralizing Antibody Against 
B/Phuket/3073/2013 (B Yamagata lineage)by Study Day and Treatment Group, 
Modified Intent to Treat Population* .......................................................................... 151 


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Figure 17: 
Reverse Cumulative Distribution of Neutralizing Antibody against 
B/Phuket/3073/2013 (B Yamagata lineage) by Study Day and Treatment Group, Per 
Protocol Population* ................................................................................................... 151 
Figure 18: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody 
against B/Brisbane/60/2008 (B Victoria lineage) by Study Day and Treatment Group, 
Modified Intent to Treat Population* .......................................................................... 151 
Figure 19: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
B/Brisbane/60/2008 (B Victoria lineage) by Study Day and Treatment Group, Per 
Protocol Population* ................................................................................................... 151 
Figure 20: 
Reverse Cumulative Distribution of Neutralizing Antibody Against 
B/Brisbane/60/2008 (B Victoria lineage) by Study Day and Treatment Group, 
Modified Intent to Treat Population* .......................................................................... 151 
Figure 21: 
Reverse Cumulative Distribution of Neutralizing Antibody against B/Brisbane/60/2008 
(B Victoria lineage) by Study Day and Treatment Group, Per Protocol Population*. 151 
Figure 22: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody Against 2017 
A/H7N9 by Study Day and Treatment Group, Modified Intent to Treat Population* 152 
Figure 23: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody against 2017 
A/H7N9 by Study Day and Treatment Group, Per Protocol Population* ................... 152 
Figure 24: 
Geometric Mean Titers of Neutralizing Antibody against 2017 A/H7N9 by Study Day 
and Treatment Group, Modified Intent to Treat Population*...................................... 152 
Figure 25: 
Geometric Mean Titers of Neutralizing Antibody against 2017 A/H7N9 by Study Day 
and Treatment Group, Per Protocol Population* ........................................................ 152 
Figure 26: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody Against 
A/Michigan/45/2015 X-275(H1N1) by Study Day and Treatment Group, Modified 
Intent to Treat Population* .......................................................................................... 152 
Figure 27: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody against 
A/Michigan/45/2015 X-275(H1N1) by Study Day and Treatment Group, Per Protocol 
Population* ................................................................................................................. 152 
Figure 28: 
Geometric Mean Titers of Neutralizing Antibody against A/Michigan/45/2015 X-
275(H1N1) by Study Day and Treatment Group, Modified Intent to Treat Population*
 ..................................................................................................................................... 152 
Figure 29: 
Geometric Mean Titers of Neutralizing Antibody against A/Michigan/45/2015 X-
275(H1N1) by Study Day and Treatment Group, Per Protocol Population* .............. 152 
Figure 30: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody Against A/Hong 
Kong/4801/2014 X263B  (H3N2) by Study Day and Treatment Group, Modified Intent 
to Treat Population* .................................................................................................... 152 
Figure 31: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody against A/Hong 
Kong/4801/2014 X263B (H3N2) by Study Day and Treatment Group, Per Protocol 
Population* ................................................................................................................. 152 
Figure 32: 
Geometric Mean Titers of Neutralizing Antibody against A/Hong Kong/4801/2014 
X263B (H3N2) by Study Day and Treatment Group, Modified Intent to Treat 
Population* ................................................................................................................. 153 
Figure 33: 
Geometric Mean Titers of Neutralizing Antibody against A/Hong Kong/4801/2014 
X263B (H3N2) by Study Day and Treatment Group, Per Protocol Population* ....... 153 
Figure 34: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody Against 
B/Phuket/3073/2013 (B Yamagata lineage) by Study Day and Treatment Group, 
Modified Intent to Treat Population* .......................................................................... 153 
Figure 35: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody against 
B/Phuket/3073/2013 (B Yamagata lineage) by Study Day and Treatment Group, Per 
Protocol Population* ................................................................................................... 153 


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Figure 36: 
Geometric Mean Titers of Neutralizing Antibody against B/Phuket/3073/2013 (B 
Yamagata lineage) by Study Day and Treatment Group, Modified Intent to Treat 
Population* ................................................................................................................. 153 
Figure 37: 
Geometric Mean Titers of Neutralizing Antibody against B/Phuket/3073/2013 (B 
Yamagata lineage) by Study Day and Treatment Group, Per Protocol Population* .. 153 
Figure 38: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody Against 
B/Brisbane/60/2008 (B Victoria lineage) by Study Day and Treatment Group, 
Modified Intent to Treat Population* .......................................................................... 153 
Figure 39: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody against 
B/Brisbane/60/2008 (B Victoria lineage) by Study Day and Treatment Group, Per 
Protocol Population* ................................................................................................... 153 
Figure 40: 
Geometric Mean Titers of Neutralizing Antibody against B/Brisbane/60/2008 (B 
Victoria lineage) by Study Day and Treatment Group, Modified Intent to Treat 
Population* ................................................................................................................. 153 
Figure 41: 
Geometric Mean Titers of Neutralizing Antibody against B/Brisbane/60/2008 (B 
Victoria lineage) by Study Day and Treatment Group, Per Protocol Population* ..... 153 
Figure 42: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against 2017 A/H7N9 by Study Day and Treatment Group, Modified Intent-to-Treat 
Population* ................................................................................................................. 154 
Figure 43: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against 2017 A/H7N9 by Study Day and Treatment Group, Per Protocol Population*
 ..................................................................................................................................... 154 
Figure 44: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against A/Michigan/45/2015 X-275(H1N1) by Study Day and Treatment Group, 
Modified Intent-to-Treat Population* ......................................................................... 154 
Figure 45: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against A/Michigan/45/2015 X-275(H1N1) by Study Day and Treatment Group, Per 
Protocol Population* ................................................................................................... 155 
Figure 46: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against A/Hong Kong/4801/2014 X263B (H3N2) by Study Day and Treatment Group, 
Modified Intent-to-Treat Population* ......................................................................... 155 
Figure 47: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against A/Hong Kong/4801/2014 X263B (H3N2) by Study Day and Treatment Group, 
Per Protocol Population* ............................................................................................. 155 
Figure 48: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against B/Phuket/3073/2013 (B Yamagata lineage) by Study Day and Treatment 
Group, Modified Intent-to-Treat Population* ............................................................. 155 
Figure 49: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against B/Phuket/3073/2013 (B Yamagata lineage) by Study Day and Treatment 
Group, Per Protocol Population* ................................................................................ 155 
Figure 50: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against B/Brisbane/60/2008 (B Victoria lineage) by Study Day and Treatment Group, 
Modified Intent-to-Treat Population* ......................................................................... 155 
Figure 51: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against B/Brisbane/60/2008 (B Victoria lineage) by Study Day and Treatment Group, 
Per Protocol Population* ............................................................................................. 155 
Figure 52: 
Maximum Severity of Solicited Systemic Symptoms per Subject by Day Post Dose 156 
Figure 53: 
Maximum Severity of Solicited Local Symptoms per Subject by Day Post Dose...... 156 
Figure 54: 
Frequency of Unsolicited Adverse Events by MedDRA® System Organ Class and 
Severity ....................................................................................................................... 157 


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Figure 55: 
Incidence of Unsolicited Adverse Events by MedDRA® System Organ Class and 
Severity ....................................................................................................................... 158 
Figure 56: 
Frequency of Adverse Events by MedDRA® System Organ Class and Relationship to 
Treatment .................................................................................................................... 159 
Figure 57: 
Incidence of Adverse Events by MedDRA® System Organ Class and Relationship to 
Treatment .................................................................................................................... 160 
Figure 58: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Laboratory 
Parameter and Treatment Group – White Blood Cells ................................................ 161 
Figure 59: 
Laboratory Summary Statistics of Change from Baseline by Parameter, Maximum 
Severity, Study Day, and Treatment Group – Hemoglobin ........................................ 161 
Figure 60: 
Laboratory Summary Statistics of Change from Baseline Results by Parameter, 
Maximum Severity, Study Day, and Treatment Group – Platelets ............................. 161 
Figure 61: 
Laboratory Summary Statistics of Change from Baseline by Parameter, Maximum 
Severity, Study Day, and Treatment Group – Alanine Aminotransferase (ALT) ....... 161 
Figure 62: 
Laboratory Summary Statistics of Change from Baseline Results by Parameter, 
Maximum Severity, Study Day, and Treatment Group – Total Bilirubin ................... 162 
Figure 63: 
Laboratory Summary Statistics of Change from Baseline Results by Parameter, 
Maximum Severity, Study Day, and Treatment Group – Creatinine .......................... 162 
 


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10.1 
Disposition of Subjects Figures 
Figure 1: 
CONSORT Flow Diagram* 
 
Allocated to Group 1 (n=x) 
♦Received allocated intervention (n=x) 
♦Did not receive allocated intervention (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Discontinued 
Intervention 
(n=x) 
 
[Reason 1] (x), [Reason 2] (x) 
Early Termination (n=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) 
Assessed for Eligibility (n=x) 
Excluded* (n=x) 
♦ [Reason 1] (n=x) 
♦ [Reason 2] (n=x) 
Randomized (n=x) 
Allocation 
Analysis 
Follow-Up 
Enrollment 
Allocated to Group 2 (n=x) 
♦Received allocated intervention (n=x) 
♦Did not receive allocated intervention (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Allocated to Group 3 (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=x) 
[Reason 1] (x), [Reason 2] (x) 
Early Termination (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) 
Analysed for immunogenicity (n=x) 
♦Excluded from immuno analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for safety (n=x) 
♦Excluded from safety analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 


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14.2.2 Immunogenicity Figures 
Figure 2: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody 
against 2017 A/H7N9 by Study Day and Treatment 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 outcome day (21, 42, 63, and 180 days post dose 1 and 
180 days post final dose). Figures generated for the preliminary report will include data from all visits 
through study Day 64. Visit labels should be included in the panel headers. Within each panel individual 
curves should be used for each Treatment Group (three curves). Each treatment group should have a 
separate color and marker shape.] 
 
Figures with similar format: 
Figure 3: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
2017 A/H7N9 by Study Day and Treatment Group, Per Protocol Population* 
Figure 4: 
Reverse Cumulative Distribution of Neutralizing Antibody Against 2017 A/H7N9 by 
Study Day and Treatment Group, Modified Intent to Treat Population* 
Figure 5: 
Reverse Cumulative Distribution of Neutralizing Antibody against 2017 A/H7N9 by 
Study Day and Treatment Group, Per Protocol Population* 
Figure 6: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody 
against A/Michigan/45/2015 X-275(H1N1) by Study Day and Treatment Group, 
Modified Intent to Treat Population* 
Figure 7: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
A/Michigan/45/2015 X-275(H1N1) by Study Day and Treatment Group, Per 
Protocol Population* 


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Figure 8: 
Reverse Cumulative Distribution of Neutralizing Antibody Against 
A/Michigan/45/2015 X-275(H1N1) by Study Day and Treatment Group, Modified 
Intent to Treat Population* 
Figure 9: 
Reverse Cumulative Distribution of Neutralizing Antibody against 
A/Michigan/45/2015 X-275(H1N1) by Study Day and Treatment Group, Per 
Protocol Population* 
Figure 10: Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody 
against A/Hong Kong/4801/2014 X263B (H3N2) by Study Day and Treatment 
Group, Modified Intent to Treat Population* 
Figure 11: Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
A/Hong Kong/4801/2014 X263B (H3N2) by Study Day and Treatment Group, Per 
Protocol Population* 
Figure 12: Reverse Cumulative Distribution of Neutralizing Antibody Against A/ Hong 
Kong/4801/2014 X263B (H3N2) by Study Day and Treatment Group, Modified 
Intent to Treat Population* 
Figure 13: Reverse Cumulative Distribution of Neutralizing Antibody against A/ Hong 
Kong/4801/2014 X263B (H3N2) by Study Day and Treatment Group, Per Protocol 
Population* 
Figure 14: Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody 
against B/Phuket/3073/2013 (B Yamagata lineage) by Study Day and Treatment 
Group, Modified Intent to Treat Population* 
Figure 15: Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
B/Phuket/3073/2013 (B Yamagata lineage) by Study Day and Treatment Group, Per 
Protocol Population* 
Figure 16: Reverse Cumulative Distribution of Neutralizing Antibody Against 
B/Phuket/3073/2013 (B Yamagata lineage)by Study Day and Treatment Group, 
Modified Intent to Treat Population* 
Figure 17: Reverse Cumulative Distribution of Neutralizing Antibody against 
B/Phuket/3073/2013 (B Yamagata lineage) by Study Day and Treatment Group, Per 
Protocol Population* 
Figure 18: Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody 
against B/Brisbane/60/2008 (B Victoria lineage) by Study Day and Treatment 
Group, Modified Intent to Treat Population* 
Figure 19: Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
B/Brisbane/60/2008 (B Victoria lineage) by Study Day and Treatment Group, Per 
Protocol Population* 
Figure 20: Reverse Cumulative Distribution of Neutralizing Antibody Against 
B/Brisbane/60/2008 (B Victoria lineage) by Study Day and Treatment Group, 
Modified Intent to Treat Population* 
Figure 21: Reverse Cumulative Distribution of Neutralizing Antibody against 
B/Brisbane/60/2008 (B Victoria lineage) by Study Day and Treatment Group, Per 
Protocol Population* 
 


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Figure 22: Geometric Mean Titers of Hemagglutination Inhibition Antibody Against 2017 
A/H7N9 by Study Day and Treatment 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 group. Each treatment group should have a separate 
color and marker shape] 
 
Note: this figure will be generated for the preliminary report including data through Day 43, then re-
generated for the final CSR to include all data through Day 202. 
 
 
Figures with similar format: 
Figure 23: Geometric Mean Titers of Hemagglutination Inhibition Antibody against 2017 
A/H7N9 by Study Day and Treatment Group, Per Protocol Population* 
Figure 24: Geometric Mean Titers of Neutralizing Antibody against 2017 A/H7N9 by Study 
Day and Treatment Group, Modified Intent to Treat Population* 
Figure 25: Geometric Mean Titers of Neutralizing Antibody against 2017 A/H7N9 by Study 
Day and Treatment Group, Per Protocol Population* 
Figure 26: Geometric Mean Titers of Hemagglutination Inhibition Antibody Against 
A/Michigan/45/2015 X-275(H1N1) by Study Day and Treatment Group, Modified 
Intent to Treat Population* 
Figure 27: Geometric Mean Titers of Hemagglutination Inhibition Antibody against 
A/Michigan/45/2015 X-275(H1N1) by Study Day and Treatment Group, Per 
Protocol Population* 
Figure 28: Geometric Mean Titers of Neutralizing Antibody against A/Michigan/45/2015 X-
275(H1N1) by Study Day and Treatment Group, Modified Intent to Treat 
Population* 
Figure 29: Geometric Mean Titers of Neutralizing Antibody against A/Michigan/45/2015 X-
275(H1N1) by Study Day and Treatment Group, Per Protocol Population* 
Figure 30: Geometric Mean Titers of Hemagglutination Inhibition Antibody Against A/Hong 
Kong/4801/2014 X263B  (H3N2) by Study Day and Treatment Group, Modified 
Intent to Treat Population* 
Figure 31: Geometric Mean Titers of Hemagglutination Inhibition Antibody against A/Hong 
Kong/4801/2014 X263B (H3N2) by Study Day and Treatment Group, Per Protocol 
Population* 


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Figure 32: Geometric Mean Titers of Neutralizing Antibody against A/Hong Kong/4801/2014 
X263B (H3N2) by Study Day and Treatment Group, Modified Intent to Treat 
Population* 
Figure 33: Geometric Mean Titers of Neutralizing Antibody against A/Hong Kong/4801/2014 
X263B (H3N2) by Study Day and Treatment Group, Per Protocol Population* 
Figure 34: Geometric Mean Titers of Hemagglutination Inhibition Antibody Against 
B/Phuket/3073/2013 (B Yamagata lineage) by Study Day and Treatment Group, 
Modified Intent to Treat Population* 
Figure 35: Geometric Mean Titers of Hemagglutination Inhibition Antibody against 
B/Phuket/3073/2013 (B Yamagata lineage) by Study Day and Treatment Group, Per 
Protocol Population* 
Figure 36: Geometric Mean Titers of Neutralizing Antibody against B/Phuket/3073/2013 (B 
Yamagata lineage) by Study Day and Treatment Group, Modified Intent to Treat 
Population* 
Figure 37: Geometric Mean Titers of Neutralizing Antibody against B/Phuket/3073/2013 (B 
Yamagata lineage) by Study Day and Treatment Group, Per Protocol Population* 
Figure 38: Geometric Mean Titers of Hemagglutination Inhibition Antibody Against 
B/Brisbane/60/2008 (B Victoria lineage) by Study Day and Treatment Group, 
Modified Intent to Treat Population* 
Figure 39: Geometric Mean Titers of Hemagglutination Inhibition Antibody against 
B/Brisbane/60/2008 (B Victoria lineage) by Study Day and Treatment Group, Per 
Protocol Population* 
Figure 40: Geometric Mean Titers of Neutralizing Antibody against B/Brisbane/60/2008 (B 
Victoria lineage) by Study Day and Treatment Group, Modified Intent to Treat 
Population* 
Figure 41: Geometric Mean Titers of Neutralizing Antibody against B/Brisbane/60/2008 (B 
Victoria lineage) by Study Day and Treatment Group, Per Protocol Population* 
 
 


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Figure 42: Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against 2017 A/H7N9 by Study Day and Treatment 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 (baseline and 21, 42, 63, and 180 days post dose 1 
and 180 days post final dose). Visit labels should be included in the panel header. Within each panel 
distinct marker types and colors should be used to indicate the treatment groups, with treatment group 
labels included in a legend. Each treatment group should have a unique color and marker shape. The 
spearman correlation should be calculated over all subjects and annotated within each panel as 
“Spearman Correlation (r=0.xx, p=0.xx)”] 
 
Figure with Similar format: 
Figure 43: Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against 2017 A/H7N9 by Study Day and Treatment Group, Per Protocol 
Population* 
Figure 44: Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against A/Michigan/45/2015 X-275(H1N1) by Study Day and Treatment Group, 
Modified Intent-to-Treat Population* 


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Figure 45: Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against A/Michigan/45/2015 X-275(H1N1) by Study Day and Treatment Group, Per 
Protocol Population* 
Figure 46: Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against A/Hong Kong/4801/2014 X263B (H3N2) by Study Day and Treatment 
Group, Modified Intent-to-Treat Population* 
Figure 47: Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against A/Hong Kong/4801/2014 X263B (H3N2) by Study Day and Treatment 
Group, Per Protocol Population* 
Figure 48: Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against B/Phuket/3073/2013 (B Yamagata lineage) by Study Day and Treatment 
Group, Modified Intent-to-Treat Population* 
Figure 49: Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against B/Phuket/3073/2013 (B Yamagata lineage) by Study Day and Treatment 
Group, Per Protocol Population* 
Figure 50: Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against B/Brisbane/60/2008 (B Victoria lineage) by Study Day and Treatment 
Group, Modified Intent-to-Treat Population* 
Figure 51: Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against B/Brisbane/60/2008 (B Victoria lineage) by Study Day and Treatment 
Group, Per Protocol Population* 
 


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14.3.1 Safety Figures 
14.3.1.1 
Solicited Adverse Events 
Figure 52: 
Maximum Severity of Solicited Systemic Symptoms per Subject by Day Post Dose 
[Implementation Note: A Generic figure is shown below. A vertical bar chart should be presented in 1 
image file with separate panels for each treatment group and dose (3 rows (treatment groups) x 3 
columns (dose #)). Axes should be labeled as follows: x-axis label: Study Day, y-axis label: Percentage 
of Subjects (%). The treatment groups should be indicated in the panel headers including “(N=X)”, 
where N = the number of subjects in the in the Safety Population who received the relevant dose. 
Subjects are counted at most once at the maximum severity across all systemic events reported for the 
specified time point] 
 
 
Figure with similar format: 
Figure 53: 
Maximum Severity of Solicited Local Symptoms per Subject by Day Post 
Dose 
 


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14.3.1.2 
Unsolicited Adverse Events 
Figure 54: 
Frequency of Unsolicited Adverse Events by MedDRA® System Organ Class 
and Severity 
[Implementation Note: A Generic figure is shown below. This figure includes all unsolicited events 
across all doses. A horizontal bar chart should be presented in 1 image file separate panels for each 
treatment group (3 columns (treatment groups)). Axes should be labeled as follows: y-axis label: System 
Organ Class, y-axis label: Number of Events. The treatment groups should be indicated in the panel 
headers including “(N=X)”, where N = the number of subjects in the in the Safety Population. The y-
axis should present all SOCs reported by at least 1 subject and an “All Events” category. Y-axis should 
be sorted with “All Events first, then in decreasing order of total incidence] 
 
 


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Figure 55: 
Incidence of Unsolicited Adverse Events by MedDRA® System Organ Class 
and Severity 
[Implementation Note: A Generic figure is shown below. This figure includes all unsolicited events 
across all doses. A horizontal bar chart should be presented in 1 image file with separate panels for each 
treatment group (3 columns). Axes should be labeled as follows: y-axis label: System Organ Class, x-
axis label: Percentage of Subjects (%). The treatment groups should be indicated in the panel headers 
including “(N=X)”, where N = the number of subjects in the in the Safety Population. Subjects are 
counted at most once at the maximum severity across for any events in the applicable SOC. The y-axis 
should present all SOCs reported by at least 1 subject and an “All Events” category. Y-axis should be 
sorted with “All Events” first then in decreasing order of total incidence]  
 
 
 


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Figure 56: 
Frequency of Adverse Events by MedDRA® System Organ Class and Relationship 
to Treatment 
[Implementation Note: A generic sample figure is shown below. This figure includes all unsolicited 
events across all doses. A horizontal bar chart should be presented in 1 image file with separate panels 
for each treatment group and study dose (3 columns (treatment groups). Axes should be labeled as 
follows: y-axis label: System Organ Class, y-axis label: Number of Events. The treatment groups should 
be indicated in the panel headers including “(N=X)”, where N = the number of subjects in the in the 
Safety Population. The y-axis should present all SOCs reported by at least 1 subject and an “All Events” 
category. Y-axis should be sorted with “All Events first  then in decreasing order of total frequency] 
 
 


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Figure 57: 
Incidence of Adverse Events by MedDRA® System Organ Class and Relationship to 
Treatment 
[Implementation Note: A Generic figure is shown below. This figure includes all unsolicited events 
across all doses. A horizontal bar chart should be presented in a 1 image file with separate panels for 
each treatment group (3 columns (treatment groups)). Axes should be labeled as follows: y-axis label: 
System Organ Class, x-axis label: Percentage of Subjects (%). The treatment groups should be indicated 
in the panel headers including “(N=X)”, where N = the number of subjects in the in the Safety 
Population. Subjects are counted at most once at the maximum relationship (related >not-related) across 
for any events in the applicable SOC. The y-axis should present all SOCs reported by at least 1 subject 
and an “All Events” category. Y-axis should be sorted with “All Events first, then in decreasing order 
of total incidence across groups]  
 
 


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14.3.5 Displays of Laboratory Results 
Figure 58: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Laboratory Parameter and Treatment Group – White Blood Cells 
[Implementation note: A generic figure is shown below. Plot should be generated with all treatment 
groups in a single image file with panels for each treatment group (3 columns (treatment groups)) with 
a box plot shown for each post-baseline study day that labs are drawn (D8, D22, D29, D43, D50). 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 59: 
Laboratory Summary Statistics of Change from Baseline by Parameter, Maximum 
Severity, Study Day, and Treatment Group – Hemoglobin 
Figure 60: 
Laboratory Summary Statistics of Change from Baseline Results by Parameter, 
Maximum Severity, Study Day, and Treatment Group – Platelets 
Figure 61: 
Laboratory Summary Statistics of Change from Baseline by Parameter, Maximum 
Severity, Study Day, and Treatment Group – Alanine Aminotransferase (ALT) 
 
 


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Figure 62: 
Laboratory Summary Statistics of Change from Baseline Results by Parameter, 
Maximum Severity, Study Day, and Treatment Group – Total Bilirubin 
Figure 63: 
Laboratory Summary Statistics of Change from Baseline Results by Parameter, 
Maximum Severity, Study Day, and Treatment Group – Creatinine 
 


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LISTINGS MOCK-UPS 
 
LIST OF LISTINGS 
Listing 1: 
16.1.6 - Listing of Subjects Receiving Investigational Product .................................. 164 
Listing 2: 
16.2.1 - Early Terminations or Discontinued Subjects ............................................... 165 
Listing 3: 
16.2.2.1 - Subject-Specific Protocol Deviations ......................................................... 166 
Listing 4: 
16.2.2.2 - Non-Subject-Specific Protocol Deviations ................................................. 167 
Listing 5: 
16.2.3 - Subjects Excluded from Analysis Populations .............................................. 168 
Listing 6: 
16.2.4.1 - Demographics Data ..................................................................................... 169 
Listing 7: 
16.2.4.2 – Pre-Existing and Concurrent Medical Conditions ...................................... 170 
Listing 8: 
16.2.4.3 – Influenza Vaccination History.................................................................... 171 
Listing 9: 
16.2.6 - Individual Immunogenicity Response Data ................................................... 173 
Listing 10:  
16.2.7.1 - Solicited Events – Systemic Symptoms ...................................................... 174 
Listing 11:  
16.2.7.2 - Solicited Events – Local Symptoms ........................................................... 175 
Listing 12: 
16.2.7.3 - Unsolicited Adverse Events ........................................................................ 176 
Listing 13: 
16.2.8.1 - Clinical Laboratory Results – Hematology ................................................. 177 
Listing 14: 
16.2.8.2 - Clinical Laboratory Results – Chemistry .................................................... 178 
Listing 15: 
16.2.9.1 - Vital Signs ................................................................................................... 179 
Listing 16: 
16.2.9.2 - Physical Exam Findings .............................................................................. 180 
Listing 17: 
16.2.10 - Concomitant Medications ............................................................................ 181 
Listing 18: 
16.2.11.1 - Pregnancy Reports – Maternal Information .............................................. 182 
Listing 19: 
16.2.11.2 - Pregnancy Reports – Gravida and Para ..................................................... 182 
Listing 20: 
16.2.11.3 - Pregnancy Reports – Live Birth Outcomes ............................................... 183 
Listing 21: 
16.2.11.4 - Pregnancy Reports – Still Birth Outcomes ............................................... 183 
Listing 22: 
16.2.11.5 - Pregnancy Reports – Spontaneous, Elective, or Therapeutic Abortion 
Outcomes..................................................................................................................... 183 
 
 


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16.1.6 Listing of Subjects Receiving Investigational Product 
Listing 1: 
16.1.6 - Listing of Subjects Receiving Investigational Product 
Subject ID 
Randomized  
Treatment Group 
Product Received Study 
Dose 1 
Product Received Study 
Dose 2 
Product Received Study 
Dose 3 
XXXXXXXXXX 
Group 1 
IIV4 / A/H7N9 
A/H7N9 
N/A 
XXXXXXXXXX 
Group 2 
IIV4 
A/H7N9 
A/H7N9 
XXXXXXXXXX 
Group 3 
IIV4 
N/A 
N/A 
 


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


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16.2.2 Protocol Deviations 
Listing 3: 
16.2.2.1 - Subject-Specific Protocol Deviations 
[Implementation Note: In the “Deviation” column, concatenate any and all “specify” fields (including visit number, etc.). If “Reason for Deviation” 
is “Other,” concatenate “specify” field, separate by a colon, e.g., “Other: Subject refusal.”] 
Subject 
ID 
Treatment 
Group 
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 
Deviation 
Start 
Date 
End Date 
Reason for 
Deviation 
Deviation 
Resulted in 
Subject 
Termination
? 
Deviation 
Affected 
Product 
Stability? 
Deviation 
Category 
Deviation 
Resolution 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
.


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


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


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


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Listing 8: 
16.2.4.3 – Influenza Vaccination History 
Subject ID 
Treatment Group 
Vaccine Type 
Month/Year Received 
Vaccination Type / Subtype 
 
 
[Inactivated/ LAIV/ 
Unknown] 
September 2017 
Seasonal Influenza Vaccination (2016-2017) 
 
 
[Inactivated/ LAIV/ 
Unknown] 
June 2017 
Non-Seasonal Influenza A Vaccine Subtype H5N8 
 
 
[Inactivated/ LAIV/ 
Unknown] 
June 2017 
Non-Seasonal Influenza Vaccinae Subtype M-001 


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


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16.2.6 Individual Immunogenicity Response Data 
Listing 9: 
16.2.6 - Individual Immunogenicity Response Data 
Subject ID 
Treatment Group 
Planned Time Point 
Actual Study 
Day 
Assay 
Strain 
Titer Replicate 1 
Titer Replicate 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.7 Adverse Events 
Listing 10:  16.2.7.1 - Solicited Events – Systemic Symptoms 
Subject ID 
Treatment Group 
Dose Number 
Post Dose Day 
Assessment1 
Symptom 
Severity 
Attributed to 
Alternate 
Etiology?2 
Alternate 
Etiology 
 
 
 
 
MA 
 
 
 
 
 
 
 
 
Clinic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 MA = Data reported by subject on the Memory Aid and reviewed by clinic staff and reported in Solicited Events eCRF. 
Clinic = Data collected by clinic staff during physical exam or symptom assessment (treatment administration record, in-clinic assessment, etc.) 
2 Grade 3 events only. 
 


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Listing 11:  16.2.7.2 - Solicited Events – Local Symptoms 
[Implementation Note: For group 1, dose 1 match the product received to symptoms reported based on the arm the product (IIV4, A/H7N) was 
received in] 
Subject ID 
Treatment Group 
Dose Number 
Product 
Received1 
Post Dose Day 
Assessment2 
Symptom 
Severity 
 
 
 
 
 
MA 
 
 
 
 
 
 
 
Clinic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 For Group 1, IIV4 and A/H7N9 vaccines are both received at Dose 1 in separate arms. 
2 MA = Data reported by subject on the Memory Aid and reviewed by clinic staff and reported in Solicited Events eCRF. 
Clinic = Data collected by clinic staff during physical exam or symptom assessment (treatment administration record, in-clinic assessment, etc.) 
 
 


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Listing 12: 16.2.7.3 - Unsolicited Adverse Events 
Adverse 
Event 
Associated 
with Dose 
# 
# of Days 
Post 
Associated 
Dose 
(Duration) 
Severity 
SAE? 
MAAE? 
PIMMC? 
Relationship 
to Study 
Treatment 
In Not 
Related, 
Alternative 
Etiology 
Action 
Taken 
with 
Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
MedDRA® 
System 
Organ 
Class 
MedDRA® 
Preferred 
Term 
Subject ID: , Treatment Group: , AE Number:  
 
 
 
 
SAE: No 
MAAE: Yes 
PIMMC: No 
 
 
 
 
 
 
 
Comments: 
Subject ID: , Treatment Group: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
Note: For additional details about SAEs, see Section 14.3.3 
 
 


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16.2.8 Individual Laboratory Measurements 
Listing 13: 16.2.8.1 - Clinical Laboratory Results – Hematology 
[Implementation Note: These listings (for hematology and chemistry) include all laboratory results, scheduled and unscheduled. These listings are 
not color-coded, but the severity should be included in parentheses after the result for abnormal results, e.g., 16.2 (Mild). The “extra” fields that are 
completed for abnormal results are not included in this listing; they are included in the listing of abnormal laboratory results that is included in the 
table shells.] 
Subject ID 
Treatment Group 
Sex 
Age 
(years) 
Planned 
Time 
Point 
Actual 
Study 
Day 
Alanine aminotransferase  
(IU/L) 
Total Bilirubin 
(mg/dL) 
Creatinine 
(mg/dL) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 14: 16.2.8.2 - Clinical Laboratory Results – Chemistry 
Subject ID 
Treatment Group 
Sex 
Age 
(years) 
Planned 
Time 
Point 
Actual 
Study 
Day 
White Blood Cell 
(103/µL) 
Hemoglobin 
(g/dL) 
Platelets 
(103/µL)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.9 Vital Signs and Physical Exam Findings 
Listing 15: 16.2.9.1 - Vital Signs 
[Implementation Note: This listing includes all vital sign assessments, scheduled and unscheduled. These listings are not color-coded, but the severity 
should be included in parentheses after the result for abnormal assessments, e.g., 100.7 (Mild).] 
Subject ID 
Treatment Group  
Planned Time 
Point 
Actual Study 
Day 
Temperature 
(°C) 
Systolic Blood 
Pressure 
(mmHg) 
Diastolic Blood 
Pressure 
(mmHg) 
Pulse 
(beats/min) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 16: 16.2.9.2 - Physical Exam Findings 
[Implementation Note: This listing includes all physical exam findings, scheduled and unscheduled. If a subject does not have any findings upon 
examination, they will not be included in this listing. If reported as an AE, display “Yes” with the AE Number in parentheses, e.g., “Yes (7)”.] 
Subject ID 
Treatment Group 
Planned 
Time Point 
Actual 
Study Day 
Body System 
Abnormal Finding 
Reported as an AE? 
(AE Number) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.10 
Concomitant Medications 
Listing 17: 16.2.10 - Concomitant Medications 
[Implementation Note: “Medication Start Day” and “Medication End Day” are relative to enrollment (which is Day 1, day before enrollment is Day 
-1). For medication start dates that are > 30 days prior to enrollment, rather than use exact study days, categorize as follows: 
• 
> 5 years prior to enrollment 
• 
1-5 years prior to enrollment 
• 
1-12 months prior to enrollment 
If ongoing, display “Ongoing” in the “Medication End Day” column. If taken for an AE or MH, display “Yes” with the AE or MH Number in 
parentheses, e.g., “Yes (7)”.] 
Subject 
ID 
Treatment 
Group 
CM 
Number 
Medication 
Medication Start 
Day 
Medication End 
Day 
Indication 
Taken for an 
AE? 
(AE Number) 
Taken for a condition 
on Medical History? 
(MH Number) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16.2.11 
Pregnancy Reports 
[Implementation Note: Only include the “Pregnancy Number” column if a subject has more than 1 pregnancy. Date of Conception will be calculated 
based on estimated delivery date. BMI will be calculated based on pre-pregnancy height and weight. Mother’s weight gain will be calculated based 
on pre-pregnancy weight and end of pregnancy weight. If a major congenital anomaly with previous pregnancy, display “Yes” and the text from the 
“specify” field, separated by a colon. If any substance use is reported, include a listing of substance use. If autopsy revealed an alternate etiology, 
display “Yes” and the text from the “specify” field, separated by a colon. If abnormality in product of conception, display “Yes” and the text from 
the “specify” field, separated by a colon.] 
Listing 18: 16.2.11.1 - Pregnancy Reports – Maternal Information 
Subject ID 
Treatment 
Group 
Pregnancy 
Number 
Study Day 
Corresponding 
to Estimated 
Date of 
Conception 
Source of 
Maternal 
Information 
Pregnancy 
Status 
Mother’s 
Pre-
Pregnancy 
BMI 
Mother’s 
Weight 
Gain 
During 
Pregnancy 
Tobacco, 
Alcohol, or 
Drug Use 
During 
Pregnancy? 
Medications 
During 
Pregnancy? 
Maternal 
Complications 
During 
Pregnancy? 
Maternal 
Complications 
During Labor, 
Delivery, or 
Post-Partum? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Maternal Complications are included in the Adverse Event listing. Medications taken during pregnancy are included in the Concomitant Medications 
Listing. 
 
Listing 19: 16.2.11.2 - Pregnancy Reports – Gravida and Para 
 
 
 
Live Births 
 
 
 
 
 
Subject 
ID 
Pregnancy 
Number 
Gravida 
Extremely 
PB1 
Very 
Early 
PB1 
Early 
PB1 
Late 
PB1 
Early 
TB2 
Full 
TB2 
Late 
TB2 
Post 
TB2 
Still 
Births 
Spontaneous 
Abortion/ 
Miscarriage 
Elective 
Abortions 
Therapeutic 
Abortions 
Major 
Congenital 
Anomaly with 
Previous 
Pregnancy? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 Preterm Birth 
2 Term Birth 
Note: Gravida includes the current pregnancy, para events do not. 
 
 


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Listing 20: 16.2.11.3 - Pregnancy Reports – Live Birth Outcomes 
Subject 
ID 
Pregnancy 
Number 
Fetus 
Number 
Pregnancy 
Outcome 
(for this 
Fetus) 
Fetal 
Distress 
During 
Labor and 
Delivery? 
Delivery 
Method 
Gestational 
Age at Live 
Birth  
Size for 
Gestational 
Age 
Apgar 
Score, 
1 
minute 
Apgar 
Score, 5 
minutes 
Cord 
pH 
Congenital 
Anomalies? 
Illnesses/ 
Hospitalizations 
within 1 Month 
of Birth? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Congenital Anomalies are included in the Adverse Event listing.  
 
Listing 21: 16.2.11.4 - Pregnancy Reports – Still Birth Outcomes 
Subject 
ID 
Date of 
Initial 
Report 
Fetus 
Number 
Pregnancy 
Outcome 
(for this 
Fetus) 
Fetal 
Distress 
During 
Labor and 
Delivery? 
Delivery 
Method 
Gestational 
Age at Still 
Birth 
Size for 
Gestational 
Age 
Cord pH 
Congenital 
Anomalies? 
Autopsy 
Performed? 
If Autopsy, 
Etiology for Still 
Birth Identified? 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 22: 16.2.11.5 - Pregnancy Reports – Spontaneous, Elective, or Therapeutic Abortion Outcomes 
Subject 
ID 
Date of Initial 
Report 
Fetus Number 
Pregnancy 
Outcome (for this 
Fetus) 
Gestational Age at 
Termination 
Abnormality in Product of 
Conception? 
Reason for Therapeutic 
Abortion