Clinical trial NCT03682120
Conditions: Avian Influenza Influenza Immunisation
Keywords: A/H7N9 Healthy Adults Immunogenicity Influenza vaccine MF59(R) adjuvant Reactogenicity Safety
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2018-11-02; Completion date: 2020-04-30
Enrollment: 372 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a randomized, double-blinded, Phase II study in healthy males and non-pregnant females, 18-64 years of age. This clinical trial is designed to assess the safety, reactogenicity, and immunogenicity of a pre-pandemic 2017 monovalent inactivated influenza A/H7N9 virus vaccine (2017 H7N9 IIV) manufactured by Seqirus Inc (Seqirus) administered at different dosages (3.75 microgram mcg, 7.5 mcg and 15 mcg of hemagglutinin (HA) per dose) given with MF59(R) adjuvant manufactured by Seqirus Inc., or without adjuvant (15 mcg of HA per dose). Phosphate buffered saline (PBS) diluent manufactured by Patheon Manufacturing Services LLC will be used to achieve certain targeted doses. Approximately 371 subjects who are in good health and meet all eligibility criteria will be randomized into one of 4 study groups. The study will be conducted at up to 7 Vaccine and Treatment Unit (VTEU) sites and will last approximately 17 months, with subject participation duration of approximately 13 months. The Primary Objectives of the study are: 1) To assess the safety and reactogenicity following receipt of two doses of 2017 H7N9 IIV administered intramuscularly (IM) at different dosages approximately 21 days apart given with or without MF59(R) adjuvant; 2) To assess the serum hemagglutinin inhibition (HAI) and neutralizing (Neut) antibody responses approximately 21 days following receipt of two doses of 2017 H7N9 IIV administered IM at different dosages approximately 21 days apart with or without MF59(R) adjuvant.

Detailed description:
This is a randomized, double-blinded, Phase II study in healthy males and non-pregnant females, 18-64 years of age. This clinical trial is designed to assess the safety, reactogenicity, and immunogenicity of a pre-pandemic 2017 monovalent inactivated influenza A/H7N9 virus vaccine (2017 H7N9 IIV) manufactured by Seqirus Inc (Seqirus) administered at different dosages (3.75 mcg, 7.5 mcg and 15 mcg of hemagglutinin (HA) per dose) given with MF59(R) adjuvant manufactured by Seqirus Inc., or without adjuvant (15 mcg of HA per dose). Phosphate buffered saline (PBS) diluent manufactured by Patheon Manufacturing Services LLC will be used to achieve certain targeted doses. Approximately 371 subjects who are in good health and meet all eligibility criteria will be randomized into one of 4 study groups. The study will be conducted at up to 7 Vaccine and Treatment Unit (VTEU) sites and will last approximately 17 months, with subject participation duration of approximately 13 months. The Primary Objectives of the study are: 1) To assess the safety and reactogenicity following receipt of two doses of 2017 H7N9 IIV administered intramuscularly (IM) at different dosages approximately 21 days apart given with or without MF59(R) adjuvant; 2) To assess the serum hemagglutinin inhibition (HAI) and Neutralizing (Neut) antibody responses approximately 21 days following receipt of two doses of 2017 H7N9 IIV administered IM at different dosages approximately 21 days apart with or without MF59(R) adjuvant.

The secondary Objectives are: 1) To assess all unsolicited non-serious Adverse Events (AEs) following receipt of two doses of a 2017 H7N9 IIV administered IM at different dosages approximately 21 days apart with or without MF59(R) adjuvant; 2) To assess medically-attended adverse events (MAAEs) including new-onset chronic medical conditions (NOCMCs), potentially immune-mediated medical conditions (PIMMCs), and all Serious Adverse Events (SAEs) following receipt of two doses of a 2017 H7N9 IIV administered IM at different dosages approximately 21 days apart with or without MF59(R) adjuvant; 3) To assess the serum HAI and Neut antibody responses approximately 7 and 21 days following receipt of a single dose, and approximately 7 days following receipt of two doses of 2017 H7N9 IIV administered IM at different dosages approximately 21 days apart with or without MF59(R) adjuvant.

Arms: arm 1: 3.75 mcg per 0.5 ml dose of 2017 A/H7N9 Inactivated Influenza Virus Vaccine (IIV) + MF59(R) adjuvant administered intramuscularly on Day 1 and Day 22. Phosphate buffered saline (PBS) diluent may be used to achieve targeted dosages. N=106 arm 2: 7.5 mcg per 0.5 ml dose of 2017 A/H7N9 Inactivated Influenza Virus Vaccine (IIV) + MF59(R) adjuvant administered intramuscularly on Day 1 and Day 22. Phosphate buffered saline (PBS) diluent may be used to achieve targeted dosages. N=106 arm 3: 15 mcg per 0.5 ml dose of 2017 A/H7N9 Inactivated Influenza Virus Vaccine (IIV) + MF59(R) adjuvant administered intramuscularly on Day 1 and Day 22. Phosphate buffered saline (PBS) diluent may be used to achieve targeted dosages. N=106 arm 4: 15 mcg per 0.5 ml dose of 2017 A/H7N9 Inactivated Influenza Virus Vaccine (IIV) unadjuvanted administered intramuscularly on Day 1 and Day 22. Phosphate buffered saline (PBS) diluent may be used to achieve targeted dosages. N=53
Interventions: intervention 1: A/H7N9 intervention 2: MF59 intervention 3: Phosphate Buffered Saline (PBS) diluent
Intervention descriptions: intervention 1: Monovalent inactivated, "subunit" influenza virus vaccine containing the HA and NA from influenza A/Hong Kong/125/2017 (H7N9) and the PB2, PB1, PA, NP, M and NS genes from A/Puerto Rico/8/1934 (H1N1). intervention 2: Microfluoridized adjuvant 59 (MF59) is an oil-in-water emulsion. intervention 3: Diluent for Influenza Virus Vaccine.

Protocol documents:
Prot_000.pdf: 
 
 
A Phase II Study in Healthy Adults 18-64 Years Old to Assess the 
Safety, Reactogenicity and Immunogenicity of a Seqirus A/H7N9 
Inactivated Influenza Vaccine Administered Intramuscularly With or 
Without MF59® Adjuvant  
DMID Protocol Number:  
17-0076 
DMID Funding Mechanism: Vaccine and Treatment Evaluation Units 
 
Pharmaceutical Support: 
Seqirus Inc. 
 
IND Sponsor: DMID, NIAID 
 
Lead Principal Investigator: Sharon E. Frey, MD 
DMID Clinical Project Manager: Robin M. Mason, MS 
Version: 3.0 
24 June 2019 
 
 


DMID Protocol 17-0076 
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STATEMENT OF ASSURANCE 
Each Institution will hold a current Federal Wide Assurance (FWA) issued by the Office of 
Human Research Protections (OHRP) for federally-funded human subjects research. Each FWA 
will designate at least one Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) registered with OHRP, for which the research will be reviewed and approved by the 
IRB/IEC and will be subject to continuing review [45 CFR 46.103(b)]. The IRB/IEC designated 
under an FWA may include an institution’s IRB/IEC, an independent IRB/IEC, or an IRB/IEC of 
another institution after establishing a written agreement with that other institution. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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STATEMENT OF COMPLIANCE 
The study 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 312 (Investigational New Drug 
Application), 21 CFR 812 (Investigational Device Exemptions) 
• 
The International Council for Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use” (ICH) E6(R2) Good Clinical Practice:  Integrated 
Addendum to ICH E6(R1) Guidance for Industry,” published in the Federal Register 
(83 Federal Register 8882 (2018)), including the latest finalized revision 
• Belmont Report:  Ethical Principles and Guidelines for the Protection of Human Subjects of 
Research, Report of the National Commission for the Protection of Human Subjects of 
Biomedical and Behavioral Research 
• National Institutes of Health (NIH) Office of Extramural Research, Research Involving 
Human Subjects, as applicable 
• National Institute of Allergy and Infectious Diseases (NIAID) Clinical Terms of Award, as 
applicable 
• Applicable Federal, State, and Local Regulations and Guidance  


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SIGNATURE PAGE 
The signature below provides the necessary assurances 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 Investigator Signature: 
 
Signed: 
 
 
Date: 
 
 
Name 
Title 
 
 
 


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TABLE OF CONTENTS 
STATEMENT OF ASSURANCE ...................................................................................................2 
STATEMENT OF COMPLIANCE .................................................................................................3 
SIGNATURE PAGE .......................................................................................................................4 
TABLE OF CONTENTS .................................................................................................................5 
LIST OF TABLES ...........................................................................................................................9 
LIST OF FIGURES .......................................................................................................................10 
LIST OF ABBREVIATIONS ........................................................................................................11 
PROTOCOL SUMMARY .............................................................................................................14 
1 
Key Roles ..............................................................................................................................20 
2 
Background Information and Scientific Rationale ...............................................................21 
 
Background ...............................................................................................................21 
 Public Readiness and Emergency Preparedness Act ....................................24 
 
Scientific Rationale ...................................................................................................25 
2.2.1 Purpose of Study ...........................................................................................25 
2.2.2 Study Population ...........................................................................................26 
 
Potential Risks and Benefits .....................................................................................26 
 Potential Risks ..............................................................................................26 
 Potential Benefits ..........................................................................................31 
3 
Study Design, Objectives and Endpoints or Outcome Measures .........................................32 
 
Study Design Description .........................................................................................32 
 
Study Objectives .......................................................................................................33 
 Primary ..........................................................................................................33 
 Secondary ......................................................................................................33 
3.2.3 Exploratory ...................................................................................................34 
 
Study Endpoints or Outcome Measures ....................................................................34 
 Primary ..........................................................................................................34 
 Secondary ......................................................................................................35 
 Exploratory ...................................................................................................36 
4 
Study intervention/investigational product ...........................................................................37 
 
Study Product Description ........................................................................................37 
4.1.1 Formulation, Storage, Packaging, and Labeling ...........................................37 
4.1.2 Product Storage and Stability........................................................................39 
4.2 
Acquisition/Distribution ...........................................................................................39 
4.3 
Dosage/Regimen, Preparation, Dispensing and Administration of Study 
Intervention/ Investigational Product ........................................................................40 
4.4 
Pre-determined Modification of Study Intervention/Investigational Product for an 
Individual Subject .....................................................................................................42 


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4.5 
Accountability Procedures for the Study Intervention/ Investigational Product(s) ..42 
5 
Selection of subjects and study Enrollment and Withdrawal ...............................................44 
 
Eligibility Criteria .....................................................................................................44 
 Subject Inclusion Criteria .............................................................................44 
 Subject Exclusion Criteria ............................................................................45 
 
Withdrawal from the Study, Discontinuation of Study Product, or Study 
Termination ...............................................................................................................48 
 Withdrawal from the Study or Discontinuation of the Study Product ..........48 
5.2.2 Subject Replacement .....................................................................................49 
5.2.3 Study Termination ........................................................................................50 
6 
Study Procedures ..................................................................................................................51 
 
Screening (Optional) Visit 00, Day -28 to -1, Clinic Visit .......................................51 
 
Enrollment, Visit 01 Day 01 for subjects previously screened at Day -28 to -1 and 
First Vaccination (Dose 1), Clinic Visit ...................................................................52 
 
Visit 01, Day 1, Enrollment/Baseline (for subjects not previously screened at Day -
28 to -1) and First Study Vaccination (Dose 1), Clinic Visit....................................54 
 
Planned Study Visits .................................................................................................56 
 Follow-up ......................................................................................................56 
 Final Study Visit, Visit 11, Day 387, Safety Follow-up, Phone Call ...........62 
 Early Termination Visit (if needed) ..............................................................62 
6.5 
Unscheduled Visit (if needed) ..................................................................................64 
6.6 
Protocol Deviations ...................................................................................................65 
7 
Description of Clinical and Laboratory Evaluations ............................................................66 
7.1 
Clinical Evaluations ..................................................................................................66 
 Assessment of Concomitant Medications/Treatments other than Study 
Product ..........................................................................................................67 
7.2 
Laboratory Evaluations .............................................................................................68 
7.2.1 Clinical Laboratory Evaluations ...................................................................68 
7.2.2 Research Assays............................................................................................68 
7.2.2.1 Laboratory Specimen Preparation, Handling, and Shipping ............69 
7.2.2.2 Laboratory Specimen Shipment ........................................................70 
8 
Assessment of safety .............................................................................................................71 
8.1 
Assessing and Recording Safety Parameters ............................................................71 
8.1.1 Adverse Events .............................................................................................71 
8.1.1.1 Adverse Events Grading ...................................................................72 
8.1.2 Reactogenicity...............................................................................................73 
8.1.3 Serious Adverse Events ................................................................................75 
8.2 
Specifications of Safety Parameters ..........................................................................77 
8.2.1 Solicited Events ............................................................................................77 
8.2.2 Unsolicited Events ........................................................................................77 


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8.2.3 Unsolicited events are any other AEs that occur following administration of 
study product. ................................................................................................77 
8.2.4 New Onset Chronic Medical Conditions (NOCMCs) ..................................77 
8.2.5 Medically Attended Adverse Events (MAAEs) ...........................................77 
8.2.6 Potentially Immune Mediated Medical Conditions (PIMMCs)....................77 
8.3 
Reporting Procedures ................................................................................................77 
8.3.1 Reporting Serious Adverse Events ...............................................................78 
8.3.2 Regulatory Reporting for Studies Conducted Under DMID Sponsored IND
.......................................................................................................................79 
8.3.3 Reporting of Pregnancy ................................................................................79 
8.3.4 Disclosure of Study Related Information .....................................................79 
8.4 
Type and Duration of Follow-up of Subjects after Adverse Events .........................79 
8.5 
Procedures to be Followed in the Event of Abnormal Laboratory Test Values or 
Abnormal Clinical Findings ......................................................................................80 
8.6 
Halting Rules ............................................................................................................81 
8.6.1 Study Halting Criteria ...................................................................................81 
8.6.2 Individual Halting Criteria ............................................................................82 
8.7 
Safety Oversight........................................................................................................84 
8.7.1 Independent Safety Monitor (ISM) ...............................................................84 
8.7.2 Data and Safety Monitoring Board (DSMB) ................................................84 
9 
Human subject protection .....................................................................................................86 
9.1 
Institutional Review Board/Independent Ethics Committee.....................................86 
9.2 
Informed Consent Process ........................................................................................86 
9.3 
Consent for Future Use of Stored Specimens and Data ............................................88 
9.4 
Exclusion of Women, Minorities, and Children (Special Populations) ....................89 
9.5 
Subject Confidentiality .............................................................................................90 
9.6 
Certificate of Confidentiality ....................................................................................90 
9.7 
Costs, Subject Compensation, and Research Related Injuries ..................................91 
10 
Statistical Considerations ......................................................................................................92 
10.1 
Study Hypotheses......................................................................................................92 
10.2 
Sample Size Considerations ......................................................................................92 
10.3 
Treatment Assignment Procedures ...........................................................................94 
10.3.1 Randomization Procedures ...........................................................................94 
10.3.2 Masking Procedures ......................................................................................94 
10.4 
Planned Interim Analyses .........................................................................................95 
10.4.1 Interim Safety Review ..................................................................................95 
10.4.2 Interim Immunogenicity or Efficacy Review ...............................................96 
10.5 
Final Analysis Plan ...................................................................................................96 
10.5.1 Analysis Populations .....................................................................................97 
10.5.2 Safety Data ....................................................................................................97 


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10.5.3 Immunogenicity Data....................................................................................98 
10.5.4 Missing Values and Outliers .........................................................................99 
11 
Source Documents Access to Source Data/Documents ......................................................100 
12 
Quality Control and Quality Assurance ..............................................................................101 
13 
Data Handling and Record Keeping ...................................................................................102 
13.1 
Data Management Responsibilities.........................................................................102 
13.2 
Data Coordinating Center/Biostatistician Responsibilities .....................................102 
13.3 
Data Capture Methods ............................................................................................102 
13.4 
Types of Data ..........................................................................................................102 
13.5 
Study Records Retention.........................................................................................103 
14 
Clinical Monitoring .............................................................................................................104 
15 
Publication Policy ...............................................................................................................105 
16 
Literature References ..........................................................................................................106 
17 
Appendices ..........................................................................................................................111 
APPENDIX A: SCHEDULE OF PROCEDURES AND EVALUATIONS ...............................112 
APPENDIX B. LIST OF POTENTIALLY IMMUNE MEDIATED MEDICAL CONDITIONS
.............................................................................................................................................116 
 
 
 


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LIST OF TABLES 
Table 1: Study Design ....................................................................................................................18 
Table 2: Venipuncture Volumes (mL): ..........................................................................................69 
Table 3: Injection Site Reactogenicity Grading .............................................................................73 
Table 4: Injection Site Reactogenicity Measurements ...................................................................74 
Table 5: Subjective Systemic Reactogenicity Grading ..................................................................74 
Table 6: Quantitative Systemic Reactogenicity Grading ...............................................................75 
Table 7: Pulse and Blood Pressure Grading for Subjects 18-64 years of age................................75 
Table 8: Power (%) to Detect Safety Events: ................................................................................92 
Table 9: Precision of Binomial Confidence Intervals: ...................................................................93 
Table 10: Minimum Detectable Difference in Proportion Responders with 80% Power ..............93 
Table 11: Lower Confidence bound2 for difference in proportion of responders between 
adjuvanted (N = 100) and unadjuvanted (N = 50) arms, 18-64 years stratum ...........93 
 
 
 
 
 
 
 
 
 
 
 
 
 


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LIST OF FIGURES 
Figure 1: Schematic of Study Design ............................................................................................19 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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LIST OF ABBREVIATIONS 
A/H1N1 
Influenza A Virus of the H1N1 Subtype 
A/H2N2 
Influenza A Virus of the H2N2 Subtype 
A/H3N2 
Influenza A Virus of the H3N2 Subtype 
A/H3N2v 
Influenza A Virus of the H3N2 Variant Subtype 
A/H5N1 
Influenza A Virus of the H5N1 Subtype 
A/H5N2 
Influenza A Virus of the H5N2 Subtype 
A/H5N6 
Influenza A Virus of the H5N6 Subtype 
A/H5N3 
Influenza A Virus of the H5N3 Subtype 
A/H5N8 
Influenza A Virus of the H5N8 Subtype 
A/H7N1 
Influenza A Virus of the H7N1 Subtype 
A/H7N7 
Influenza A Virus of the H7N7 Subtype 
A/H7N9 
Influenza A Virus of the H7N9 Subtype 
A/H9N2 
Influenza A Virus of the H9N2 Subtype 
AS03 
Adjuvant System 03 
AdvantageEDCSM 
Electronic Data Capture System 
AE 
Adverse Event/Adverse Experience 
ALT 
Alanine Aminotransferase 
AESIs 
Adverse Events of Special Interest 
ANCA 
Anti-Neutrophil Cytoplasmic Antibody 
BARDA 
Biomedical Advanced Research and Development Authority 
BMI 
Body Mass Index 
BP 
Blood Pressure 
BPM 
Beats Per Minute 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
CICP 
Countermeasure Injury Compensation Program 
CMS 
Clinical Materials Services 
CoA 
Certificate of Analysis 
CROMS 
Clinical Research Operations and Management Support 
Cr 
Creatinine 
CSL 
Commonwealth Serum Laboratories 
CSR 
Clinical Study Report 
CTAB 
Cetyltrimethylammonium bromide 
°C 
Degrees Celsius 
°F 
Degrees Fahrenheit 
D 
Day(s) 


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DCC 
Data Coordinating Center 
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 
FDA 
Food and Drug Administration 
FWA 
Federal Wide 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 
HIV 
Human Immunodeficiency Virus 
HPAI 
Highly Pathogenic Avian Influenza 
HRSA 
Health Resources and Services Administration 
IATA 
International Air Transport Association 
IB 
Investigator’s Brochure 
ICD 
International Classification of Diseases 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IgG 
Immunoglobulin G 
IIV 
Inactivated Influenza Virus 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 


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mL 
Milliliter(s) 
mmHg 
Millimeters of Mercury 
MOP 
Manual of Procedures 
N 
Number of Subjects 
NA 
Neuraminidase 
Neut 
Neutralizing or Neutralization 
NI 
Neuraminidase Inhibiting  
NIAID 
National Institute of Allergy and Infectious Diseases, NIH, 
DHHS 
NIH 
National Institutes of Health 
NSAIDs 
Non-Steroidal Anti-Inflammatory Drugs 
NOCMCs 
New-Onset Chronic Medical Conditions 
NVD 
Novartis Vaccines and Diagnostics 
OER 
Office of Extramural Research 
OHRP 
Office for Human Research Protections 
OTC 
Over the Counter 
PBS 
Phosphate Buffered Saline 
PHI 
Personal Health Information 
PIMMCs 
Potentially Immune-Mediated Medical Conditions 
PLT 
Platelets 
PP 
Per Protocol 
PREP Act 
Public Readiness and Emergency Preparedness Act 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
T. Bili 
Total Bilirubin 
US 
United States 
V 
Visit(s) 
VTEU 
Vaccine and Treatment Evaluation Unit 
WBC 
White Blood Cells 
WHO 
World Health Organization 


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PROTOCOL SUMMARY 
Title: 
A Phase II Study in Healthy Adults 18-64 Years Old to Assess the 
Safety, Reactogenicity and Immunogenicity of a Seqirus A/H7N9 
Inactivated Influenza Vaccine Administered Intramuscularly With 
or Without MF59® Adjuvant  
Design of the Study: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
This is a randomized, double-blinded, Phase II study in healthy 
males and non-pregnant females, 18-64 years of age. This clinical 
trial is designed to assess the safety, reactogenicity, and 
immunogenicity of a pre-pandemic 2017 monovalent inactivated 
influenza A/H7N9 virus vaccine (2017 H7N9 IIV) manufactured 
by Seqirus Inc (Seqirus) administered at different dosages (3.75 
microgram [mcg], 7.5 mcg and 15 mcg of hemagglutinin (HA) per 
dose) given with MF59® adjuvant manufactured by Seqirus Inc. 
(Seqirus), or without adjuvant (15 mcg of HA per dose). 
Phosphate buffered saline (PBS) diluent manufactured by Patheon 
Manufacturing Services LLC will be used to achieve certain 
targeted doses. The 2017 H7N9 inactivated influenza vaccine 
(IIV) was manufactured using a reverse genetics-derived 
reassortant candidate vaccine virus IDCDC RG56B (H7N9), 
containing the HA and neuraminidase (NA) from low pathogenic 
influenza A/Hong Kong/125/2017 (H7N9) and the PB2, PB1, PA, 
NP, M and NS from A/Puerto Rico/8/1934 (H1N1).  
Subjects who are in good health and meet all eligibility criteria 
(including a negative serum or urine pregnancy test for women of 
childbearing potential, history and physical exam) within 28 days 
prior to the first vaccination or on the day of, but prior to, first 
vaccination, will be randomized into one of 4 study groups as 
shown in Table 1. Baseline blood samples for 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 adverse events (AEs) will be collected 
from the time of each study vaccination through approximately 21 
days after each study vaccination. Serious adverse events (SAEs), 


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Study Phase: 
medically-attended adverse events (MAAEs), including new-onset 
chronic medical conditions (NOCMCs), and potentially immune-
mediated medical conditions (PIMMCs), will be collected from 
the time of 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 hemagglutinin 
inhibition (HAI) and neutralizing (Neut) antibody assays against 
the 2017 H7N9 vaccine virus on serum samples obtained 
immediately prior to each study vaccination (Days 1 and 
approximately Day 22), approximately 7 days after each study 
vaccination (Days 8 and 29), and approximately 21 and 180 days 
after the second study vaccination (Days 43 and 202). 
Novel methods for identifying and assessing alternative correlates 
of protection against influenza infection are needed.  We will 
assess the NA-specific antibody response to vaccination. In 
addition, we plan to determine the NA content of IIV using assays 
that are currently under development. If successful, we will 
determine whether the NA content correlates with the N9 NA-
specific antibody response in a dosage-specific manner. If NA 
content of the vaccine is not determined, then we will determine 
whether the NA-specific antibody response increases with 
increasing dosage of vaccine based on the HA content. 
Subjects who have not received the current season’s licensed   
seasonal trivalent or quadrivalent influenza vaccine prior to 
enrollment may receive it anytime following completion of the 
Day 43 study visit or upon early termination. 
 
II 
Study Population: 
Approximately 371 individuals 18-64 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 7 Vaccine and Treatment Evaluation Unit (VTEU) sites 


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Description of Study 
Product or Intervention: 
Two doses delivered intramuscularly (IM) approximately 21 days 
apart of a monovalent inactivated pre-pandemic influenza A/H7N9 
vaccine (2017 H7N9 Inactivated Influenza Vaccine [IIV]) 
manufactured by Seqirus, at different dosages [3.75, 7.5 or 15 
micrograms/0.5 milliliter (mL) of hemagglutinin (HA) from 
A/Hong Kong/125/2017 H7N9 vaccine per dose] administered 
with MF59® adjuvant (Seqirus) or without adjuvant [15 
microgram (mcg) HA per dose]. 
Phosphate buffered saline (PBS) diluent manufactured by Patheon 
Manufacturing Services LLC is added to monovalent vaccine to 
achieve targeted HA content. 
Study Objectives: 
 
Primary: 
Safety: 
• To assess the safety and reactogenicity following receipt of 
two doses of 2017 H7N9 IIV administered IM at different 
dosages approximately 21 days apart given with or without 
MF59® adjuvant  
Immunogenicity: 
• To assess the serum HAI and Neut antibody responses 
approximately 21 days following receipt of two doses of 
2017 H7N9 IIV administered IM at different dosages 
approximately 21 days apart with or without MF59® 
adjuvant. 
Secondary: 
Safety: 
• To assess all unsolicited non-serious AEs following receipt 
of two doses of a 2017 H7N9 IIV administered IM at 
different dosages approximately 21 days apart with or 
without MF59® adjuvant  
• To assess MAAEs including NOCMCs, PIMMCs, and all  
SAEs following receipt of two doses of a 2017 H7N9 IIV 
administered IM at different dosages approximately 21 
days apart with or without MF59® adjuvant 
Immunogenicity: 


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• To assess the serum HAI and Neut antibody responses 
approximately 7 and 21 days following receipt of a single 
dose, and approximately 7 days following receipt of two 
doses of 2017 H7N9 IIV administered IM at different 
dosages approximately 21 days apart with or without 
MF59® adjuvant. 
Exploratory: 
Immunogenicity: 
• To assess the effects of age, sex, body mass index, and 
prior receipt of seasonal influenza vaccine(s) on serum 
HAI and Neut antibody responses following receipt of two 
doses of a 2017 H7N9 IIV administered IM at different 
dosages approximately 21 days apart with or without 
MF59® adjuvant. 
• To assess, in at least a subset of samples, the cross-
reactivity of serum HAI and Neut antibody responses to 
antigenically drifted variants of influenza A/H7 viruses 
following receipt of two doses of a 2017 H7N9 IIV 
administered IM at different dosages approximately 21 
days apart with or without MF59® adjuvant.  
• To assess the durability of serum HAI and Neut antibody 
responses at approximately 180 days following receipt of 
two doses of 2017 H7N9 IIV administered IM at different 
dosages approximately 21 days apart with or without 
MF59® adjuvant.  
• To assess the NA content of the 2017 H7N9 IIV and 
determine the serum antibody responses to NA following 
receipt of 2017 H7N9 IIV. 
 
 
 
 
 
Duration of Individual 
Subject Participation: 
Approximately thirteen (13) months 


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Estimated Time to Last 
Subject/Last Study Day: 
Approximately seventeen (17) months 
Table 1: Study Design 
Treatment Arms1 
Day 1 
Day 22 
Group 1, n=106 
Seqirus H7N9 vaccine 3.75 mcg 
plus MF59® adjuvant 
Seqirus H7N9 vaccine 3.75 mcg 
plus MF59® adjuvant 
Group 2, n=106 
Seqirus H7N9 vaccine 7.5 mcg 
plus MF59® adjuvant 
Seqirus H7N9 vaccine 7.5 mcg 
plus MF59® adjuvant 
Group 3, n=106 
Seqirus H7N9 vaccine 15 mcg 
plus MF59® adjuvant 
Seqirus H7N9 vaccine 15 mcg 
plus MF59® adjuvant 
Group 4, n=53 
Seqirus H7N9 vaccine 15 mcg 
unadjuvanted 
Seqirus H7N9 vaccine 15 mcg 
unadjuvanted 
 
1 Randomization will be stratified by site and prior receipt of at least one of the 2017-2018 
and/or 2018-2019 seasonal influenza vaccine. No target number of participants is identified for 
each prior vaccination stratum. 




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1 
KEY ROLES 
 
Lead Principal Investigator: 
 
 
 
 
Sharon Frey, MD 
Saint Louis University School of Medicine 
 
 
DMID Clinical Project Manager: 
Robin M. Mason, MS 
Division of Microbiology and Infectious Diseases 
NIAID, NIH 
 
Data Coordinating Center: 
The Emmes Company, LLC 
 
 
 
 
 
 
 


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2 
BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE 
 
Background  
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 hemagglutinin (HA) protein in the vaccine, the 
number and intervals of doses administered, the addition of immune stimulating components 
(i.e., adjuvants), and the manufacturing methods used to produce the vaccine (i.e., whole virus, 
split virus, or purified surface antigen). Host-specific factors, including the recipient’s age, their 
prior influenza infections and/or vaccinations, and the presence of underlying diseases and their 
treatments, all can influence the immune responses elicited by an influenza vaccine. 
Serum antibodies targeting the influenza virus HA and 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 support 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 
seasonal IIVs contain 7.5 mcg or 15 mcg of HA antigen per vaccine strain (for children aged <36 
months) or 15 mcg of HA antigen per vaccine strain (for persons aged ≥36 months). Clinical 
studies evaluating increased HA-containing influenza vaccines performed over the past 35 years 
have shown dose-related increases in serum and mucosal antibody responses [14-22]. Higher HA 
dosage vaccines can lead to enhanced antibody responses in the elderly [23]. In 2009, a high-
dose IIV containing 4 times the standard HA antigen per seasonal vaccine strain was approved in 
the United States (US) for use in individuals 65 years of age and older.  
In general, clinical studies evaluating vaccines made from novel avian influenza viruses (e.g., 
A/H5N1, A/H7N7) suggest that these vaccines are substantially less immunogenic than those 
from other novel subtypes (e.g., 2009 A/H1N1 pandemic virus, even when administered at high 
HA dosages [24, 25]). Due to the poor immunogenicity of H5 and H7 vaccines, the inclusion of 
adjuvants was evaluated to assess their ability to boost anti-viral serum immunoglobulin G (IgG) 
levels. In the United States, aluminum salts are licensed as adjuvants in combination with several 
vaccines; however, their use in subvirion influenza A/H5N1 vaccines has shown either no effect 
or a very modest enhancement of immune responses compared to non-aluminum salt containing 
formulations [26-28]. In contrast, the use of oil-in-water emulsion adjuvants, most notably 
proprietary adjuvants AS03 and MF59® produced by GlaxoSmithKline Biologicals (GSK) and 
Seqirus, respectively, has resulted in increased antibody responses to IIVs containing novel HAs 
in numerous clinical trials [29-32].  
Since 1997, MF59®, an oil-in-water adjuvant used in the seasonal influenza vaccine (FLUAD®) 
has been licensed for use in elderly individuals 65 years of age and older in 32 countries. Since 
then, FLUAD® has been licensed for children in several countries including South Africa (12 
years of age and older), Mexico (6 to 36 months of age) and Canada (6 to less than 24 months).  
FLUAD® has been licensed in the US (65 years of age and older) since November 2015 (see 
Section 2.3.1). Clinical trials performed to assess the safety, immunogenicity and efficacy of 
novel HA-containing IIV formulations with and without MF59® reported that antibody GMTs 
and seroconversion rates were significantly higher among recipients of the adjuvanted vaccine 
compared to recipients of non-adjuvanted formulations [33-34].   
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, 


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as well as MF59® adjuvants. The National Institute of Allergy and Infectious Diseases (NIAID) 
has conducted several clinical trials to evaluate avian influenza (A/H9N2, 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 [35-41]. In response to emerging H5N8 viruses that 
have caused extensive outbreaks in domestic poultry and wild birds in South East Asia [42, 43], 
NIAID has recently completed enrollment for two 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 [43], 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 March 2018 a total of 
1,567 laboratory-confirmed human infections with avian influenza A/H7N9 virus have been 
reported by the World Health Organization [44, 45]. Whereas most cases have been centered in 
and around mainland China, there have been several travel-associated cases, including two in 
travelers reported by Canada who were returning from China in early 2015 [46]. 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 [45]. 
Laboratory studies have shown that A/H7N9 influenza viruses readily infect cells from human 
respiratory tract tissue samples and can spread from ferret to ferret by droplet transmission, 
thereby increasing the concern about the pandemic potential of these viruses [47, 48]. 
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 [45]. 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 [44, 49].  
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 


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H7N9 vaccines for the U.S. stockpile and for an assessment of its safety and immunogenicity in 
clinical trials. 
 
Public Readiness and Emergency Preparedness Act 
For this protocol, the study products monovalent inactivated influenza 2017 H7N9 virus vaccine 
manufactured by Seqirus and adjuvant (MF59®) manufactured by Seqirus 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. 
An individual who suffers a serious physical injury or death from administration and use of the 
2017 H7N9 IIV with or without adjuvant may request benefits from the CICP. A serious physical 
injury means an injury that is life threatening, results in, or requires, medical or surgical 
intervention to prevent permanent impairment of a body function, or permanent damage to body 
structure. The CICP is the payer of last resort.  This means that it only covers expenses or 
provides benefits that other third-party payers, such as health insurance, the Department of 
Veterans Affairs, or Workers’ Compensation programs don’t have an obligation to pay. 
If no funds have been appropriated to the compensation program, the Secretary of HRSA does 
not make a final determination on the individual’s request within 240 days, or if the individual 
decides not to accept the compensation, the injured individual or his representative may pursue a 
tort claim in the US District Court for the District of Columbia, but only if the claim involves 
willful misconduct, is pled with particularity required under the PREP Act, verified, and 
accompanied by an affidavit by a physician who did not treat the individual and certified medical 
records. Any award is reduced by any public or private insurance or worker’s compensation 
available to the injured individual. Awards for non-economic damages, such as pain, suffering, 


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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. 
 
Scientific Rationale 
2.2.1 
Purpose of Study 
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 Seqirus, respectively. In 
general, these trials have demonstrated that adjuvant use results in a significant dose-sparing 
effect. NIAID has recently completed enrollment of two “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 [45, 49]. To date, no cases of H7N9 from the new lineage have been identified in 
birds or people infected outside of China; however, a few cases have been identified in Hong 
Kong and Taiwan in infected travelers returning from China. Importantly, antigenic analysis of 
the fifth wave H7N9 viruses and serology studies indicate that the stockpiled H7N9 vaccine 
manufactured several years ago does not induce protective HAI or Neut antibodies against the 
Yangtze River Delta lineage. Hence, there is broad consensus across HHS and interagency 
leadership that a new vaccine should be developed that would be effective against the currently 
predominating H7N9 viruses.  
Several candidate vaccine viruses are under evaluation by the Center for Disease Control (CDC) 
and the World Health Organization (WHO) H5 Reference Laboratories Network.  Under contract 
to BARDA/DHHS, Seqirus has produced a monovalent inactivated influenza pre-pandemic 2017 
A/H7N9 virus vaccine (2017 H7N9 IIV). The availability of the US Government-stockpiled 
MF59® (Seqirus) oil-in-water adjuvant provides an opportunity to determine if dose-sparing 


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effects occur when mixing the Seqirus 2017 H7N9 vaccine with the MF59® adjuvant (See 
Section 4.1 for additional details on the H7N9 vaccine). 
The goal of this clinical trial is to assess the safety, reactogenicity and immunogenicity of two 
doses of the 2017 H7N9 IIV administered with or without MF59® in healthy adults.  The 2017 
H7N9 IIV manufactured by Seqirus will be administered IM at different dosages mixed at the 
site with MF59® [3.75, 7.5 and 15 mcg HA per dose) or given without MF59® (15 mcg HA per 
dose) to evaluate the dose-sparing potential of the adjuvant. Data from phase I clinical trials of 
avian IIVs suggest that they are poorly immunogenic and require multiple high-doses or the 
inclusion of an adjuvant to induce serum HAI titer of 40 or greater against the study vaccine 
virus. In previous NIAID- sponsored clinical trials of 2013 H7N9 IIV, 2 doses of non-adjuvanted 
15 or 45 mcg of HA per dose did not confer significant seroprotection [37, 39].  In addition to 
assessing antigen-sparing strategies, another goal of this study is to assess, in at least a subset of 
samples, whether serum IgG elicited by the 2017 H7N9 IIV recognizes 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-response relationship of NA 
content with elicited humoral antibody responses to the N9 NA [50]. 
Based on previously conducted studies with a 2013 H7N9 IIV manufactured by Sanofi 
administered with or without MF59®, we anticipate that two doses of the 2017 H7N9 IIV 
administered IM at different dosages with MF59® adjuvant approximately 21 days apart will be 
well-tolerated and more immunogenic compared to the non-adjuvanted vaccine in healthy adult 
individuals [37, 51]. 
2.2.2 
Study Population 
The study population will be representative of the general public from each of the VTEU 
participating sites.  Children will not be included as this study is designed for healthy adult 
subjects between the ages of 18-64 years. 
 
Potential Risks and Benefits 
 
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 2017 H7N9 IIV, with or without PBS diluent and/or 
MF59® adjuvant, and breach of confidentiality. 


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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 risk to subjects who report that they are in good health but who have an 
unknown health problem at the time of vaccination.  This trial will screen by physical exam, 
history, and vital signs. To minimize the risk, subjects will not receive the second study 
vaccination if the subject meets any of the exclusion criteria listed in Section 8.6.2. 
There is potential for AEs to occur more frequently in the adjuvanted vaccine groups [32] 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 2017 
H7N9 IIV 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 has sponsored five Phase II clinical 
trials to assess the safety, reactogenicity, and immunogenicity of one or two IM doses of a 
monovalent A/H7N9 vaccine produced by Sanofi Pasteur, Swiftwater, PA, administered with or 
without AS03 or MF59® in healthy subjects (DMID Protocols: 13-0032, NCT01938742; 13-
0033, NCT01942265; 13-0034, NCT02213354; 13-0044, NCT02586792; and 14-0015, 
NCT02921997). Overall, the study products administered in these clinical trials were generally 
safe and well-tolerated. For DMID Protocol 13-0032, nine SAEs were reported. All were 
assessed as being not related to study product. Two AEs of special interest (AESIs) were 
reported in this clinical trial: Hashimoto’s disease (assessed as not related to study product) and 
Hashimoto’s thyroiditis (assessed as related to study product). For DMID Protocol 13-0033, 
sixteen SAEs were reported, fifteen of these SAEs were assessed as being not related to study 
product. One SAE was considered to be related: acute inferior myocardial infarction. Two 
AESIs were reported in this clinical trial: psoriasiform dermatitis and celiac disease (both 
assessed as not related to study product because both disorders pre-existed to vaccination, but 
both disorders received the diagnosis after vaccination). 
 
The manufacturing process used to produce the monovalent 2017 H7N9 IIV is the same as for 
the US licensed product Agriflu® seasonal influenza vaccine with the exception of the final steps 
being performed at the Parkville manufacturing site, which is an FDA-approved manufacturing 
site for Afluria®, but not Agriflu®. The current H7N9 monovalent subunit IIV to be used in this 
trial was derived from the influenza virus A/Hong Kong/125/2017 (H7N9). The potential risks to 
subjects are anticipated to be similar to those observed for Seqirus’ unadjuvanted, licensed 
seasonal IIV, Agriflu® (see Agriflu® Package Insert). 


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Occasionally, adult recipients of unadjuvanted licensed, IIVs may develop influenza-like 
reactions, such as fever, feverishness, fatigue, malaise, myalgia, arthralgia, headache, and/or 
nausea. Some subjects may develop reactions at the injection site, including pruritus, and/or 
ecchymosis due to the vaccination procedure, erythema, induration/swelling, pain, and/or 
tenderness [53].  
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 licensed vaccine. These reactions 
can manifest as hives, angioedema, bronchospasm, tachycardia, or 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 
vaccination, typically with onset within 6 weeks after vaccination [54]. Interestingly, although 
vaccination rates have increased in the last 10 years, the numbers of reported cases of vaccine-
associated GBS have declined [55]. 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 
[56]. An active, population-based surveillance study conducted in the United States during the 


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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 [57-59]. Another study using the Medicare system showed an elevated 
risk of GBS with 2009 H1N1 vaccination (incidence rate ratio = 2.41, 95% confidence interval: 
1.14, 5.11; attributable risk = 2.84 per million doses administered, 95% confidence interval: 0.21, 
5.48) [60]. An international collaboration study also supported a conclusion of an association 
between 2009 H1N1 vaccination and GBS [61]. It is unknown if the administration of the 2017 
H7N9 IIV to be used in this clinical trial will result in an increased incidence of GBS as the 
mechanism leading to this AE has not been completely elucidated. 
Numerous studies have shown that the MF59® adjuvant significantly improved the 
immunogenicity of inactivated subunit influenza virus vaccines, with a clinically acceptable 
increase in the incidence of injection site reactions [33-35, 37, 39-41, 51, 62-64].There was, as 
expected, a general tendency for an increased risk of slightly more mild and transient solicited 
injection site (especially tenderness/pain) and systemic reactions in subjects exposed to MF59®, 
while there was a consistent indication for a similar or decreased overall risk of all unsolicited 
AEs, autoimmune diseases, new onset of chronic diseases, cardiovascular diseases, SAEs, 
hospitalizations, and deaths, when compared to non MF59®-adjuvanted influenza vaccines. 
Additional information can be found in the FDA-licensed FLUAD® package insert. 
Subjects should be informed that they might experience the following injection site and systemic 
AEs after vaccination with MF59®-adjuvanted vaccines: 
Injection site reactions: redness, swelling, pain, ecchymosis, induration.   
Systemic reactions: fever, malaise, chills, fatigue, headache, sweating, myalgia, arthralgia, 
shivering.   
Most reactions are mild or moderate and resolve spontaneously within one to two days.  
The following adverse events have been spontaneously reported during post-approval use of 
FLUAD® in the United States since March 2017 (package insert). Because these events are 
reported voluntarily from a population of uncertain size, it is not always possible to reliably 
estimate their frequency or establish a causal relationship to the vaccine. 
 
Blood and lymphatic system disorders: Thrombocytopenia (some cases were severe with platelet 
counts less than 5,000 per mm3), lymphadenopathy  
General disorders and administration site conditions: Extensive swelling of injected limb lasting 
more than one week, injection site cellulitis-like reactions (some cases of swelling, pain, and 
redness extending more than 10 cm and lasting more than 1 week)  
 


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Immune system disorders:  Allergic reactions including anaphylactic shock, anaphylaxis and 
angioedema  
 
Musculoskeletal and connective tissue disorders: Muscular weakness  
 
Nervous system disorders: Encephalomyelitis, Guillain-Barré Syndrome, convulsions, neuritis, 
neuralgia, paraesthesia, syncope, presyncope  
 
Skin and subcutaneous tissue disorders:  Generalized skin reactions including erythema 
multiforme, urticaria, pruritis or non-specific rash  
 
Vascular disorders: Vasculitis with transient renal involvement 
There is substantial clinical experience with MF59® adjuvant. In a very extensive set of clinical 
studies, MF59® has proven to be an effective vaccine adjuvant with an acceptable safety and 
tolerability profile, resulting in the licensure of an MF59®-adjuvanted interpandemic seasonal 
subunit IIV3 (FLUAD®) in 32 countries worldwide including the US (US licensed since 
November 2015). FLUAD® was initially licensed for commercial sale in 1997 in Italy, and is 
currently approved with either a Mutual Recognition Procedure or a National Procedure in 11 
EU countries. It is also currently registered for use in 19 other countries worldwide. This 
adjuvanted vaccine is currently licensed for immunization of elderly people 65 years of age and 
above (with the exceptions in South Africa, where FLUAD® is licensed in subjects 12 years of 
age and above, and in Canada where FLUAD® is licensed for use in both adults 65 years of age 
and older and children ≥6 to <24 months of age).   
It is unknown if the Seqirus 2017 H7N9 IIV (A/Hong Kong/125/2017) with or without MF59® 
adjuvant poses any risks to an unborn child. Tsai et al. evaluating the clinical trial database of all 
Novartis vaccine studies from 1991-2009 found that the distribution of pregnancy outcomes 
(normal, abnormal, or ending in induced abortion) were similar in subjects exposed to MF59®-
adjuvanted and non-adjuvanted influenza vaccines at any time in pregnancy [65]. In a 
comparative cohort study, Heikkinen et al. found no differences in gestational diabetes, 
preeclampsia, stillbirth, low birth weight, neonatal deaths, or congenital malformations among 
MF59-adjuvanted A/H1N1 vaccinated and unvaccinated cohorts [66]. 
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 


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this trial will not use information that will identify subjects by name. Organizations that may 
inspect and/or copy research records maintained at the participating VTEU sites for quality 
assurance and data analysis include groups such as the local Institutional Review Board (IRB), 
NIAID, and the FDA. 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by US Law. This web site will not include information that can identify subjects.  
There may be other risks, discomforts, or side effects that are unknown at this time. 
 
Potential Benefits 
Vaccination using the 2017 H7N9 IIV with or without MF59® adjuvant may or may not provide 
protection against a serious disease with the 2017 H7N9 IIV, should the participant be exposed. 
The duration of any such protection is currently unknown. The 2017 H7N9 IIV with or without 
MF59® 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 DESIGN, OBJECTIVES AND ENDPOINTS OR 
OUTCOME MEASURES 
 
Study Design Description 
This is a randomized, double-blinded, Phase II study in 371 healthy males and non-pregnant 
females, 18-64 years of age. This clinical trial is designed to assess the safety, reactogenicity, 
and immunogenicity of a pre-pandemic 2017 H7N9 IIV manufactured by Seqirus administered at 
different dosages (3.75 mcg, 7.5 mcg and 15 mcg of HA per dose, n=106 per arm) given with 
MF59® adjuvant manufactured by Seqirus, or without adjuvant (15 mcg of HA per dose, n=53). 
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 genes from 
A/Puerto Rico/8/1934 (H1N1). Phosphate buffered saline (PBS) diluent manufactured by 
Patheon Manufacturing Services LLC will be used to achieve certain targeted dosages. 
Subjects who are in good health and meet all eligibility criteria (including a negative serum or 
urine pregnancy test for women of childbearing potential, history and physical exam) within 28 
days prior to the first vaccination or on the day of, but prior to, first vaccination, will be 
randomized into one of 4 study groups as shown in Table 1. Baseline bloods samples for clinical 
safety laboratories will be drawn prior to the first vaccine dose and will not be used to screen 
subjects for eligibility. 
Reactogenicity will be measured by the occurrence of solicited injection site and systemic 
reactions from the time of each study vaccination through 7 days after each study vaccination. 
Unsolicited non-serious AEs will be collected from the time of each study vaccination through 
approximately 21 days after each study vaccination. SAEs, MAAEs, including NOCMCs, and 
PIMMCs, will be collected from the time of the first study vaccination through approximately 12 
months after the last study vaccination. Clinical laboratory evaluations for safety will be 
performed on venous blood collected prior to each study vaccination and approximately 7 days 
after each study vaccination. 
Immunogenicity testing will include performing HAI and Neut antibody assays against the 2017 
H7N9 vaccine virus on serum samples obtained immediately prior to each study vaccination 
(Days 1 and approximately Day 22), approximately 7 days after each study vaccination (Days 8 
and 29), and approximately 21 and 180 days after the second study vaccination (Days 43 and 
202). 
Novel methods for identifying and assessing alternative correlates of protection against influenza 
infection are needed.  We will assess the dose related response of NA-specific antibody to 


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vaccination.  In addition, if an assay becomes available, we plan to determine the NA content of 
inactivated influenza vaccine. If possible, we will determine whether the NA content in a dosage-
specific manner correlates with the N9 NA-specific antibody response. If NA content of the 
vaccine is not determined, then we will determine whether the NA-specific antibody response 
increases with increasing dosage of vaccine based on the HA content. 
Subjects who have not received the current season’s licensed seasonal IIV3 or IIV4 prior to 
being enrolled in the study may receive it anytime following completion of the Day 43 study 
visit or upon early termination.  
For additional details on study procedures and evaluations and study schedule by study 
visits/days, see Sections 6 and 7 and APPENDIX A: SCHEDULE OF PROCEDURES AND 
EVALUATIONS. 
 
Study Objectives 
 
Primary 
Safety: 
• To assess the safety and reactogenicity following receipt of two doses of 2017 H7N9 IIV 
administered IM at different dosages approximately 21 days apart given with or without 
MF59® adjuvant  
Immunogenicity: 
• To assess the serum HAI and Neut antibody responses approximately 21 days following 
receipt of two doses of 2017 H7N9 IIV administered IM at different dosages approximately 
21 days apart with or without MF59® adjuvant. 
 
Secondary  
Safety: 
• To assess all unsolicited non-serious AEs following receipt of two doses of a 2017 H7N9 IIV 
administered IM at different dosages approximately 21 days apart with or without MF59® 
adjuvant  
• To assess MAAEs including NOCMCs, PIMMCs, and all SAEs following receipt of two 
doses of a 2017 H7N9 IIV administered IM at different dosages approximately 21 days apart 
with or without MF59® adjuvant  


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Immunogenicity: 
• To assess the serum HAI and Neut antibody responses approximately 7 and 21 days 
following receipt of a single dose, and approximately 7 days following receipt of two doses 
of 2017 H7N9 IIV administered IM at different dosages approximately 21 days apart with or 
without MF59® adjuvant. 
3.2.3 
Exploratory 
Immunogenicity: 
• To assess the effects of age, sex, body mass index, and prior receipt of seasonal influenza 
vaccine(s) on serum HAI and Neut antibody responses following receipt of two doses of a 
2017 H7N9 IIV administered IM at different dosages approximately 21 days apart with or 
without MF59® adjuvant. 
• To assess, in at least a subset of samples, the cross-reactivity of serum HAI and Neut 
antibody responses to antigenically drifted variants of influenza A/H7 viruses following 
receipt of two doses of a 2017 H7N9 IIV administered IM at different dosages approximately 
21 days apart with or without MF59® adjuvant.  
• To assess the durability of serum HAI and Neut antibody responses at approximately 180 
days following receipt of two doses of 2017 H7N9 IIV administered IM at different dosages 
approximately 21 days apart with or without MF59® adjuvant.  
• To assess the NA content of the 2017 H7N9 IIV and determine the serum antibody responses 
to NA following receipt of 2017 H7N9 IIV. 
 
Study Endpoints or Outcome Measures 
 
Primary 
Safety: 
• Occurrence of study vaccine-related SAEs from the time of the first study vaccination 
through approximately 12 months after the last study vaccination. 
• Occurrence of solicited injection site and systemic reactogenicity events from the time of 
each study vaccination through 7 days after each study vaccination. 


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• Occurrence of clinical safety laboratory adverse events from the time of each study 
vaccination through approximately 7 days after each study vaccination. 
Immunogenicity: 
• For HAI and Neut antibodies, percentage of subjects achieving seroconversion against the 
influenza 2017 H7N9 study vaccine strain (defined as either a pre-vaccination titer <10 and a 
post-vaccination titer ≥40 or a pre-vaccination titer ≥10 and a minimum four-fold rise in 
post-vaccination titer) at approximately 21 days after the second study vaccination (Study 
Day 43). 
• For HAI and Neut antibodies, percentage of subjects achieving titer ≥40 against the influenza 
2017 H7N9 study vaccine strain at approximately 21 days after the second study vaccination 
(Study Day 43). 
• GMTs of serum HAI and Neut antibodies against the influenza 2017 H7N9 vaccine strain at 
approximately 21 days after the second study vaccination (Study Day 43).  
 
Secondary 
Safety: 
• Occurrence of study vaccine-related unsolicited non-serious AEs from the time of each study 
vaccination through approximately 21 days after each study vaccination. 
• Occurrence of all unsolicited adverse events, regardless of the assessment of seriousness or 
relatedness, from the time of each study vaccination through approximately 21 days after 
each study vaccination.  
• Occurrence of MAAEs, including NOCMCs, and PIMMCs from the time of the first study 
vaccination through approximately 12 months after the last study vaccination. 
• Occurrence of all SAEs, regardless of the assessment of relatedness, from the time of 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 
influenza 2017 H7N9 vaccine strain at approximately 7, 21, and 28 days after the first study 
vaccination (Study Day 8, 22, 29). 


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• For HAI and Neut antibodies, percentage of subjects achieving titers of 40 or greater against 
the influenza 2017 H7N9 vaccine strain at baseline and approximately 7, 21, and 28 days 
after the first study vaccination (Study Day 8, 22, 29). 
• GMTs of serum HAI and Neut antibodies against the influenza 2017 H7N9 vaccine virus at 
baseline and approximately 7, 21, and 28 days after the first study vaccination (Study Day 8, 
22, 29).  
 
Exploratory 
Immunogenicity: 
• For HAI and Neut antibodies, percentage of subjects achieving seroconversion and the GMTs 
of serum HAI antibody against the 2017 H7N9 study vaccine strain approximately 21 and 
180 days after the second study vaccination (Study Day 43 and 202), stratified by sex, body 
mass index, and prior receipt of seasonal influenza vaccine(s). 
• For HAI and Neut antibodies, for at least a subset of subjects, percentage achieving 
seroconversion, percentage with titer ≥40, and GMTs against antigenically drifted variants of 
influenza A/H7 viruses at baseline and approximately 21 and 180 days after the second study 
vaccination (Study Day 43 and 202). 
• For HAI and Neut antibodies, percentage of subjects achieving seroconversion, percentage 
with titer ≥40, and GMTs against the 2017 H7N9 study vaccine strain at approximately 180 
days after the second study vaccination (Study Day 202). 
Percentage of subjects with detectable levels of serum N9 NA-specific antibody elicited by 2017 
H7N9 vaccination.  Serum N9 NA-specific antibody responses elicited by H7N9 vaccination will 
be correlated with NA content (if NA content results are available) at baseline and approximately 
7 and 21 days after the first study vaccination (Study Day 1, 8 and 22) and 7, 21 and 180 days 
after the second study vaccination (Study Day 29, 43 and 202). If the NA content of the vaccine 
is not determined, then we will determine whether the NA-specific antibody response increases 
with increasing dosage of vaccine based on the HA content. 
 


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4 
STUDY INTERVENTION/INVESTIGATIONAL 
PRODUCT 
 
Study Product Description 
2017 H7N9 IIV 
Seqirus has developed an H7N9 monovalent inactivated, “subunit” influenza virus vaccine, 2017 
H7N9 IIV manufactured from a reverse genetics-derived reassortant virus (A/Hong 
Kong/125/2017[H7N9]-PR8-IDCDC-RG56B) containing the HA and NA from influenza 
A/Hong Kong/125/2017 (H7N9) and the PB2, PB1, PA, NP, M and NS genes from A/Puerto 
Rico/8/1934 (H1N1). The manufacturing process for this monovalent 2017 H7N9 IIV is similar 
to the US-approved Agriflu seasonal influenza vaccine with the exception of the final steps being 
performed at the Parkville manufacturing site, which is an FDA-approved manufacturing site for 
Afluria®, but not Agriflu®. 
 
 
 
 
 
 
 
 
 
MF59® Adjuvant  
 
  
PBS Diluent 
The PBS diluent was manufactured by Patheon Manufacturing Services LLC in accordance with 
Good Manufacturing Practice Regulations. 
4.1.1 
Formulation, Storage, Packaging, and Labeling 
2017 H7N9 IIV 
The 2017 H7N9 IIV is provided as a clear, sterile, buffered aqueous solution containing 
primarily the outer membrane proteins, HA and NA and preservative in a 5 mL clear, Type 1 


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borosilicate glass, multi-dose vial. For the purposes of this protocol, each vial will be used as a 
single entry, single dose vial.   
Each multi-dose vial contains thimerosal, a mercury derivative, added as a preservative.  Each 
0.5 mL dose of non-adjuvanted vaccine contains approximately 50 mcg of thimerosal. The vials 
containing study product must be stored at 2°C to 8°C (36°F to 46°F). Do not freeze.  No 
component of this vaccine contains latex.  
 
 
 
 
 
 
 
Specific mixing instructions are included in the MOP to achieve specific dosages. 
The 2017 H7N9 IIV doses administered with adjuvant will be admixed with MF59® resulting in 
administration of an adjuvanted 2017 H7N9 IIV. 
PBS Diluent 
 It is essentially clear and slightly opalescent in color 
and must be stored at 2°C to 8°C (36°F to 46°F). Vials will be provided with latex free stoppers.  
MF59® Adjuvant [Microfluoridized Adjuvant 59]  
 
 
 
 
 The product is available in single-use vial.  The vials containing study product 
must be stored at 2°C to 8°C (36°F to 46°F), protected from light. Do not freeze.  


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Each of these study products will be labeled according to manufacturer specifications and 
include the statement “Caution: New Drug Limited by Federal Law to Investigational Use.” 
Further details are included in the respective, applicable Investigator’s Brochures for the 
Monovalent 2017 H7N9 A/Hong Kong/125/2017 Vaccine (IIV) and package insert for MF59® 
adjuvant, as well as in the protocol-specific MOP. 
Sterile empty vials will be provided with latex-free stoppers. 
4.1.2 
Product Storage and Stability  
The temperature of the storage unit must be manually recorded daily (excluding non-business 
days and holidays as applicable) and continuously monitored and recorded during the duration of 
this trial per the participating VTEU site standard operating procedures (SOPs), and 
documentation will be maintained. If the temperature fluctuates outside of the required range, the 
affected study product(s) must be quarantined at the correct storage temperature and labeled as 
‘Do Not Use’ (until further notice). The research pharmacist must alert the site PI and study 
coordinator, if the temperature fluctuates outside of the required range. In the event the 
temperature fluctuates outside of the required range, including accidental deep-freezing or 
disruption of the cold chain, the affected study product(s) must not be administered. The site PI 
or responsible person should immediately contact the DMID Product Support Team at 
DMIDProductSupportTeam@niaid.nih.gov for further instructions before any additional study 
vaccinations are administered. Based on the information collected, DMID and/or the 
manufacturer will determine whether the affected study product(s) can be used. If it cannot be 
used, the site will receive specific instructions on how to return the affected study product(s) to 
the DMID CMS or destroy it on site.  
4.2 
Acquisition/Distribution 
2017 H7N9 IIV  
2017 H7N9 IIV will be provided by Seqirus under contract to BARDA/DHHS. 
MF59® Adjuvant  
MF59® will be provided by Seqirus under contract to BARDA/DHHS. 
Upon request by DMID, 2017 H7N9 IIV, MF59® adjuvant will be transferred to the following 
address: 
 
 


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DMID Clinical Materials Services Contract 
Fisher BioServices 
20439 Seneca Meadows Parkway 
Germantown, MD 20876 
 
 
PBS diluent and sterile empty vials (2-mL, 3-mL or 5-mL) for admixing will be obtained by the 
DMID Clinical Materials Services (CMS) Contract, Fisher BioServices. 
2017 H7N9 IIV, MF59® adjuvant, PBS diluent, and sterile empty vials for study vaccine 
preparation will be provided through the DMID CMS to the participating VTEU sites prior to the 
start of this trial upon request and with prior approval from DMID. Should the site PI require 
additional 2017 H7N9 IIV, MF59® adjuvant, PBS diluent or sterile empty vials during this trial, 
further instructions are provided in the protocol-specific MOP. 
4.3 
Dosage/Regimen, Preparation, Dispensing and Administration of 
Study Intervention/ Investigational Product 
Dosage calculations are based on the actual HA content per 0.5 mL. Each 0.5 mL dose of 
MF59®-adjuvanted study vaccine contains one dose (0.25 mL) of MF59® adjuvant. 
See the protocol-specific MOP Appendices for detailed information on the preparation, labeling, 
storage, and administration of study vaccine for each treatment arm. Study vaccine preparation 
will be performed by the participating VTEU site research pharmacist on the same day of study 
vaccine administration. 
Visually inspect the 2017 H7N9 IIV, PBS diluent and MF59® 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 PI or responsible person 
should immediately contact the DMID Product Support Team at 
DMIDProductSupportTeam@niaid.nih.gov and DMID Clinical Project Manager for further 
instructions before any additional study vaccinations are administered. Based on the information 
collected, DMID and/or the manufacturer will determine whether the affected study product(s) 
can be used. If it cannot be used, the site will receive specific instructions on how to return the 
affected study product(s) to the DMID CMS or destroy it on site. If the 2017 H7N9 IIV vaccine 
PBS diluent or the MF59® adjuvant is unusable, study personnel will use another vial from the 


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study supply. Replacement vials may be requested by contacting DMID. Additional instructions 
for quarantine and DMID contact information are provided in the protocol-specific MOP. 
For those doses that must be admixed, with PBS diluent, visually inspect the 2017 H7N9 IIV 
plus PBS diluent admixture (intermediate or final mixed vial depending on treatment arm) prior 
to use. The 2017 H7N9 IIV plus PBS diluent admixture will be essentially clear and slightly 
opalescent in color. For those doses that must be admixed with PBS diluent and MF59 adjuvant, 
visually inspect the 2017 H7N9 IIV/PBS diluent plus MF59 adjuvant admixture (final mixed 
vial) prior to use. The 2017 H7N9 IIV/plus PBS admixture will be milky (whitish to yellowish) 
in appearance. If the admixture appears 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 admixture. The affected admixture must be quarantined at 2°C to 8°C (36°F to 46°F) 
for the 2017 H7N9 IIV plus PBS diluent admixture or room temperature for the 2017 H7N9 
IIV/PBS diluent plus MF59 adjuvant and labeled as ‘Do Not Use’ (until further notice).  The site 
PI or responsible person should immediately contact the DMID Product Support Team at 
DMIDProductSupportTeam@niaid.nih.gov and DMID CPM for further instructions before any 
additional study vaccinations are administered. Based on the information collected, DMID 
and/or the manufacturer will determine whether the affected admixture can be used. If it cannot 
be used, the site will receive specific instructions on how to send the affected admixture to the 
DMID CMS or destroy it on site. If the affected admixture is unusable, the participating VTEU 
sites’ research pharmacist will prepare another admixture. Additional instructions for quarantine 
and DMID contact information are provided in the protocol-specific MOP. 
For those doses that must be admixed with PBS diluent, the 2017 H7N9 IIV plus PBS diluent 
admixture, (intermediate or final mixed vial depending on treatment arm), once mixed, must be 
stored at 2°C to 8°C (36°F to 46°F) in an upright position and must be used within 8 hours. For 
those doses that must be admixed with PBS diluent and MF59 adjuvant, the 2017 A/H7N9 
IIV/PBS diluent plus MF59 adjuvant admixture (final mixed vial), once mixed, must be stored at 
room temperature in an upright position and must be used within 8 hours. 
Only one- 0.5 mL dose of study vaccine should be withdrawn from the intermediate and final 
mixed vial(s). Gently shake the intermediate and final mixed vial(s) immediately before the 
single 0.5 mL dose of study vaccine is withdrawn. 
Study vaccine administration will be performed by an unblinded study personnel member who is 
credentialed to administer vaccines and may also participate in dose preparation, but will not be 
involved in study-related assessments or have subject contact for data collection following study 
vaccine administration. Each dose of study vaccine will be administered via a single IM injection 
given in the deltoid muscle of the subjects’ preferred arm. The site of injection (right or left arm) 
will be recorded on the appropriate data collection form. Aseptic technique will be used for the 
withdrawal and administration of each dose of study vaccine using a disposable sterile needle 


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appropriate in length for each subject and a disposable sterile 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.  
4.4 
Pre-determined Modification of Study Intervention/Investigational 
Product for an Individual Subject 
There will be no dose modifications. If a subject’s second study vaccination is deferred, it should 
be rescheduled to occur within the acceptable protocol-specified window for that visit (Day 22+7 
days post first study vaccination). No exceptions to the protocol-specified window will be made. 
4.5 
Accountability Procedures for the Study Intervention/ 
Investigational Product(s) 
After receipt of the 2017 H7N9 IIV, PBS diluent, MF59® adjuvant, and sterile empty vials, the 
site PI is responsible for study product distribution and disposition, and has ultimate 
responsibility for study product accountability. The site PI will delegate to the participating 
VTEU sites’ research pharmacist responsibility for study product accountability. The 
participating VTEU sites’ research pharmacist will be responsible for maintaining complete 
records and documentation of study product receipt, accountability, dispensation, storage 
conditions, and final disposition of the study product(s). The study product accountability 
records and dispensing logs will also capture vial numbers, including final mixed vial number, 
date of study vaccine preparation/administration, time of study vaccine preparation, expiration of 
study vaccine preparation, time study vaccine is drawn into the syringe, and amount of study 
vaccine withdrawn for administration. Time of study vaccine administration to the subject will 
be captured on the appropriate data collection form. All study product(s), including the amount 
of 2017 H7N9 IIV, PBS diluent, MF59® adjuvant, and admixture, whether administered or not, 
must be documented on the appropriate study product accountability record or dispensing log. 
The sponsor's monitoring staff will verify the participating VTEU sites’ study product 
accountability records and dispensing logs per the site monitoring plan. 
Used and unused vials of 2017 H7N9 IIV, PBS diluent, MF59® adjuvant, and admixture will be 
retained until monitored and released for disposition as applicable. This can occur on an ongoing 
basis for used vials of 2017 H7N9 IIV, PBS diluent, MF59® adjuvant, and admixture. Used vials 
of A/H7N9 vaccine, PBS diluent, MF59® 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 
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DMID and communicated to the participating VTEU sites by the DMID Clinical Project 
Manager. 


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5 
SELECTION OF SUBJECTS AND STUDY 
ENROLLMENT AND WITHDRAWAL 
Approximately 371, 18-64 year old males and non-pregnant females who are in good health by 
history and meet all eligibility criteria, will be enrolled at up to 7 VTEU sites participating in this 
trial. The target population should reflect the community at large at each of the participating 
VTEU sites. Estimated time to complete enrollment in this trial is approximately 12 weeks. 
Information regarding this trial may be provided to potential subjects who have previously 
participated in vaccine trials conducted at the participating VTEU sites. Other forms and/or 
mechanisms of recruitment may also be used. The local Institutional Review Board (IRB) will 
approve all materials prior to use. 
Subject Inclusion and Exclusion Criteria must be assessed by a study clinician licensed to make 
medical diagnoses and listed on the Form FDA 1572 as the site principal investigator (PI) or sub-
investigator. 
No exemptions are granted on Subject Inclusion or Exclusion Criteria in DMID-sponsored 
studies. Questions about eligibility should be directed toward the DMID Medical Officer. 
 
Eligibility Criteria 
 
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, 18-64 years of age, inclusive. 
4. Are in good health1. 
1As determined by physical examination and medical history to evaluate acute or currently ongoing chronic medical 
diagnoses or conditions, defined as those that have been present for at least 90 days, which would affect the assessment of 
the safety of subjects or the immunogenicity of study vaccinations. Chronic medical diagnoses or conditions should be stable 
for the last 60 days (no hospitalizations, ER, or urgent care for condition and no adverse symptoms that need medical 
intervention such as medication change/supplemental oxygen). This includes no change in chronic prescription medication, 
dose, or frequency as a result of deterioration of the chronic medical diagnosis or condition in the 60 days prior to 
enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or that is done 
for financial reasons, as long as in the same class of medication, will not be considered a deviation of this inclusion 


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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 opinion of the site principal investigator or appropriate sub-
investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity and do not 
indicate a worsening of medical diagnosis or condition. Similarly, medication changes subsequent to enrollment and study 
vaccination are acceptable provided there was no deterioration in the subject’s chronic medical condition that necessitated 
a medication change, and there is no additional risk to the subject or interference with the evaluation of responses to study 
vaccination. Note: Topical, nasal, and inhaled medications (with the exception of inhaled corticosteroids as outlined in the 
Subject Exclusion Criteria (see Section 5.1.2), herbals, vitamins, and supplements are permitted. 
5. Oral temperature is less than 100.0°F. 
6. Pulse is 47 to 100 bpm, inclusive. 
7. Systolic blood pressure is 85 to 150 mmHg, inclusive. 
8. Diastolic blood pressure is 55 to 95 mmHg, inclusive. 
9. Women of childbearing potential2 must agree to practice 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 male or female condoms with spermicide or with the use of applied spermicide, 
intrauterine devices, NuvaRing®, and licensed hormonal methods such as implants, injectables, or oral contraceptives (“the 
pill”). 
10. Women of childbearing potential must have a negative serum or urine pregnancy test within 
24 hours prior to study vaccination. 
 
Subject Exclusion Criteria 
Subjects eligible to participate in this trial must not meet any of the following exclusion criteria: 
1. Have an acute illness4, as determined by the site PI or appropriate sub-investigator, within 72 
hours prior to study vaccination. 
4An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the 
site 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 PI or appropriate sub-
investigator, is a contraindication to study participation5. 


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5Including acute or chronic medical disease or condition, defined as persisting for at least 90 days, that would place the 
subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may 
interfere with the evaluation of responses or the subject’s successful completion of this trial. 
3. Have immunosuppression as a result of an underlying illness or treatment, a recent history or 
current use of immunosuppressive or immunomodulating disease therapy.  
4. Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study 
vaccination. 
5. Have known active neoplastic disease or a history of any hematologic malignancy. Non-
melanoma, treated, skin cancers are permitted. 
6. Have known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection. 
7. Have known hypersensitivity or allergy to eggs, egg or chicken protein, neomycin, 
kanamycin, formaldehyde, polysorbate 80, cetyltrimethylammonium bromide (CTAB), 
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 history of GBS. 
10. Have a history of convulsions or encephalomyelitis within 90 days prior to study vaccination. 
11. Have a history of PIMMCs6 
6Refer to Appendix B. List of Potentially Immune Mediated Medical Conditions  
12. Have a history of alcohol or drug abuse within 5 years prior to study vaccination. 
13. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric 
diagnosis that may interfere with subject compliance or safety evaluations. 
14. 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. 
15. Have taken oral or parenteral (including intra-articular) corticosteroids of any dose within 30 
days prior to study vaccination. 
16. Have taken high-dose inhaled corticosteroids7 within 30 days prior to each study vaccination. 
7High-dose defined as per age as using inhaled high dose per reference chart  
https://www.nhlbi.nih.gov/files/docs/guidelines/asthma qrg.pdf  


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17. 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. 
18. Received or plan to receive a licensed, inactivated, vaccine (excluding all flu vaccines) 
within 14 days before or after each study vaccination.  
19. Received or plan to receive seasonal IIV within 21 days before or after each study 
vaccination.  
20. Received immunoglobulin or other blood products (with exception of Rho D 
immunoglobulin) within 90 days prior to each study vaccination. 
21. 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. 
22. 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. 
23. Received or plan to receive an influenza A/H7 vaccine11 or have a history of influenza A/H7 
subtype infection.  
11And assigned to a group receiving influenza A/H7 vaccine, does not apply to documented placebo recipients. 
24. 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.  
25. Occupational exposure to or substantial direct physical contact13 with birds in the past year 
and through the 21 days after the second 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. 
26. Female subjects who are breastfeeding at any given time from the first study vaccination 
until 30 days after the last study vaccination. 


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27. Plan to travel outside the US (continental US, Hawaii, and Alaska) from enrollment through 
21 days after the second study vaccination. 
28. Receipt of Multimeric-001 (M-001) vaccine. 
 
Withdrawal from the Study, Discontinuation of Study Product, or 
Study Termination 
 
Withdrawal from the Study or Discontinuation of the Study Product 
Subjects may voluntarily withdraw their consent for trial participation at any time without 
penalty or loss of benefits to which they are otherwise entitled.   
An investigator may also withdraw a subject from receiving the study product for any reason.  
Follow-up safety evaluations will be conducted, if the subject agrees. If the subject withdraws or 
is withdrawn prior to completion of the study, the reason for this decision must be recorded in 
the case report forms (CRFs). 
The reasons, might include, but are not limited to the following: 
• Subject no longer meets eligibility criteria (see Section 5.1 and 8.6.2). 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. 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. 
• Subject meets individual halting criteria (see Section 8.6.2). 
• Subject becomes noncompliant. 
• Subject withdrawal of consent. 
• Subject lost to follow-up. 
• Termination of this trial. 
• Subject becomes pregnant, if applicable. 
• New information becomes available that makes further participation unsafe. 


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• Determined by a physician’s discretion to require additional therapy not indicated in the 
protocol to ensure subject’s health and well-being (or treatment failure, if applicable). 
• As deemed necessary by the investigator for other reasons. 
The primary reason for withdrawal from this trial will be recorded on the Study Status data 
collection form. Subjects will be encouraged to complete the Early Termination Visit. The Early 
Termination Visit procedures are listed in Section 6.4.3. 
Although subjects are free to withdraw at any time or may be withdrawn by the investigator at 
any time, those subjects who receive only one dose of study vaccine will be encouraged to 
remain in this trial for follow-up safety assessments (may be conducted by phone call rather than 
in person) continuing through approximately 12 months after their last study vaccination. These 
subjects will also be encouraged to provide a venous blood sample for immunogenicity assays at 
approximately 7 days and 21 days after their last study vaccination, if applicable. See the 
protocol-specific Manual of Procedures (MOP) for alternate follow-up requirements. 
Every attempt will be made to follow all AEs, including solicited injection site and systemic 
reactions, unsolicited non-serious AEs, SAEs, MAAEs, including NOCMCs, and PIMMCs, 
ongoing at the time of early withdrawal through resolution as per applicable collection times 
defined for the specific type of AE. 
In the case of subjects who fail to appear for a follow-up safety assessment, efforts (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. 
The investigator will inform the subject that already collected data will be retained and analyzed 
even if the subject withdraws from this study. 
5.2.2 
Subject Replacement 
Subjects who sign the informed consent form (ICF), and are randomized and vaccinated, and 
subsequently withdraw, or are withdrawn or terminated from this study, or are lost to follow-up 
will not be replaced. If subjects withdraw, or are withdrawn or terminated from the study, or are 
lost to follow-up after signing the ICF and randomization but before receipt of study vaccine, 
additional subjects may be enrolled and randomized for replacement. 


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5.2.3 
Study Termination  
If the study is prematurely terminated by the sponsor, any regulatory authority, or the 
investigator for any reason, the investigator will promptly inform the study subjects and assure 
appropriate therapy or follow-up for the subjects, as necessary. The investigator will provide a 
detailed written explanation of the termination to the IRB/IEC. 


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6 
STUDY PROCEDURES 
Complete study schedule details listed by type of visit are described below. Refer also to 
APPENDIX A: SCHEDULE OF PROCEDURES AND EVALUATIONS. 
 
Screening (Optional) Visit 00, Day -28 to -1, Clinic Visit 
• Subjects will be provided with a description of this trial (purpose and study procedures) and 
asked to read and sign the ICF. The ICF will be signed prior to performing any study 
procedures, including administration of the first study vaccination. 
• Demographic information will be obtained by interview of subjects. 
• Eligibility criteria will be reviewed with subjects. 
• Complete medical history will be obtained by interview of subjects to ensure eligibility. 
• All concomitant medications taken within 60 days prior to signing the 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 current (2018-2019) and 
previous two seasons (2016-2017 and 2017-2018), what type (inactivated or live attenuated), 
and approximate date of vaccination will be recorded on the appropriate data collection form, 
if known. Prior receipt of licensed seasonal influenza vaccine is not exclusionary, as long as 
it has been administered within the allowable window (see Section 5.1.2). 
• Subject receipt of non-seasonal influenza vaccines, including those that are experimental, 
what type (inactivated or live attenuated), what subtype (e.g., A/H3, A/H5, A/H9) and 
approximate date of vaccination will be recorded on the appropriate DCF, if known. Prior 
receipt of non-seasonal influenza vaccines are not exclusionary, except influenza A/H7 
vaccines (see Section 5.1.2). 
• Vital signs, including oral temperature, pulse, and blood pressure, will be obtained to ensure 
eligibility prior to first study vaccination. Subjects must not eat or drink anything hot or cold, 
or smoke within 10 minutes prior to taking oral temperature. 
• 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 PI or sub-investigator. 
• A serum or urine pregnancy test may be performed on all women of childbearing potential. 
Results must be negative to ensure eligibility. 
 
Enrollment, Visit 01 Day 01 for subjects previously screened at Day -
28 to -1 and First Vaccination (Dose 1), Clinic Visit 
• Subject’s willingness to participate will be reconfirmed and documented in the subject’s 
study records prior to performing any further study procedures, including administration of 
the first study vaccination. 
• Eligibility criteria will be reviewed prior to administration of the first study vaccination to 
ensure continued eligibility.  
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects prior to the study vaccination and any changes since the previous clinic visit or 
contact will be noted. 
• All concomitant medications will be reviewed with subjects prior to the first study 
vaccination for accuracy and completeness. Any new concomitant medications taken since 
the screening visit will be reviewed with subjects and assessed for continued eligibility prior 
to the first study vaccination.  
• Vital signs, including oral temperature, pulse, and blood pressure, will be obtained to ensure 
eligibility prior to first study vaccination. Vital signs assessed on Day 1 prior to the first 
study vaccination will be considered as baseline. Subjects must not eat or drink anything hot 
or cold, or smoke within 10 minutes prior to taking oral temperature. 
• A targeted physical examination, including an assessment for signs suggestive of PIMMCs, 
may be performed prior to the first study vaccination, if indicated based on review of 
complete medical history and any updates obtained by interview of subjects since the 
screening visit, by a study clinician licensed to make medical diagnoses and listed on the 
Form FDA 1572 as the site PI or sub-investigator. 


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• A serum or urine pregnancy test will be performed within 24 hours prior to the first study 
vaccination on all women of childbearing potential. Results must be negative and known 
prior to randomization and first study vaccination. 
• Subjects will be enrolled in AdvantageEDCSM and assigned randomly to a treatment arm 
prior to the first study vaccination. 
• Pre-administration reactogenicity assessments will be performed prior to the first study 
vaccination to establish baseline.  
• Approximately 10 mL of venous blood will be collected immediately prior to the first study 
vaccination for baseline serum antibody assays. 
• Approximately 10 mL of venous blood will be collected immediately prior to the first study 
vaccination for baseline clinical safety labs (WBC, Hgb, PLT, ALT, T. Bili, and Cr), and 
performed by the central (clinical) laboratory. The results from this blood draw will not be 
available or reviewed prior to study vaccination, and will serve as a safety baseline 
assessment only. 
• Approximately 10 mL of venous blood will be collected prior to study vaccination for future 
research from subjects who consent to collection of serum for future use either by signing an 
ICF that includes collection of future use samples as a condition of study participation or by 
indicating that they can opt in to sample collection for future use if the ICF allows the option 
to choose that option. 
• Subjects will then receive a single dose of study vaccine via IM injection into the deltoid 
muscle of the preferred arm. The site of injection (right or left arm) and time of 
administration will be recorded on the appropriate data collection form. Subjects will be 
observed in the clinic for at least 20 minutes after the first study vaccination. The first study 
vaccination site will be examined, post-administration reactogenicity assessments will be 
performed, and any AE/SAEs will be recorded on the appropriate data collection form prior 
to discharge from the clinic. 
• Subjects will be provided with a Memory Aid and other study-related materials to record 
daily oral temperature, solicited injection site and systemic reactions, any unsolicited AEs, 
and concomitant medications. Subjects will be encouraged to take their oral temperature 
around the same time each day. Subjects must not eat or drink anything hot or cold, or smoke 
within 10 minutes prior to taking oral temperature. Subjects will be instructed on how to use 
their Memory Aid and how to measure and record AEs prior to discharge from the clinic. 
Subjects will be instructed to notify the study center if they develop any severe reactions 
after the first study vaccination. If the site PI or appropriate sub-investigator deems the 


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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. 
• Subjects may be re-screened if they have an acute illness, present with scheduling conflicts, 
have abnormal vital sign(s), or have any other issue that the investigator thinks is acceptable 
to postpone receipt of study product to another date. 
 
Visit 01, Day 1, Enrollment/Baseline (for subjects not previously 
screened at Day -28 to -1) and First Study Vaccination (Dose 1), 
Clinic Visit 
• Subjects will be provided with a description of this trial (purpose and study procedures) and 
asked to read and sign the ICF. The ICF will be signed prior to performing any study 
procedures, including administration of the first study vaccination. 
• Demographic information will be obtained by interview of subjects. 
• Complete medical history will be obtained by interview of subjects prior to the first study 
vaccination to ensure eligibility. 
• All concomitant medications taken within 60 days prior to signing the ICF will be reviewed 
with subjects. Medications reported in the eCRF are limited to those taken within 30 days 
prior to the first study vaccination. 
• Subject receipt of licensed seasonal influenza vaccine over the current (2018-2019) and 
previous two seasons (2016-2017 and 2017-2018), what type (inactivated or live attenuated), 
and approximate date of vaccination will be recorded on the appropriate data collection form, 
if known. Prior receipt of licensed seasonal influenza vaccine is not exclusionary, as long as 
it has been administered within the allowable window (see Section 5.1.2). 
• Subject receipt of non-seasonal influenza vaccines, including those that are experimental, 
what type (inactivated or live attenuated), what subtype (e.g., A/H3, A/H5, A/H9) and 
approximate date of vaccination will be recorded on the appropriate DCF, if known. Prior 
receipt of non-seasonal influenza vaccines are not exclusionary, except influenza A/H7 
vaccines (see Section 5.1.2). 
• Vital signs, including oral temperature, pulse, and blood pressure, will be obtained to ensure 
eligibility prior to first study vaccination. Vital signs assessed on Day 1 prior to the first 
study vaccination will be considered as baseline. Subjects must not eat or drink anything hot 
or cold, or smoke within 10 minutes prior to taking oral temperature. 


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• Height and weight will be collected prior to the first study vaccination for the calculation of 
BMI. 
• A physical examination will be performed on all subjects to include the following organs and 
organ systems: skin, head and neck, lungs, heart, liver, spleen, extremities, lymph nodes, 
abdomen, general appearance, musculoskeletal and nervous system and as assessment for 
signs suggestive of a PIMMC, by a study clinician licensed to make medical diagnoses and 
listed on the Form FDA 1572 as the site PI or sub-investigator. 
• Eligibility criteria will be reviewed with subjects prior to the first study vaccination to ensure 
continued eligibility. 
• A serum or urine pregnancy test will be performed within 24 hours prior to the first study 
vaccination on all women of childbearing potential. Results must be negative and known 
prior to randomization and first study vaccination. 
• Subjects will be enrolled in AdvantageEDCSM and assigned randomly to a treatment arm 
prior to the first study vaccination. 
• Pre-administration reactogenicity assessments will be performed prior to the first study 
vaccination to establish baseline.  
• Approximately 10 mL of venous blood will be collected immediately prior to the first study 
vaccination for baseline serum antibody assays. 
• Approximately 10 mL of venous blood will be collected immediately prior to the first study 
vaccination for baseline clinical safety labs (WBC, Hgb, PLT, ALT, T. Bili, and Cr), and 
performed by the central (clinical) laboratory. The results from this blood draw will not be 
available or reviewed prior to study vaccination, and will serve as a safety baseline 
assessment only. 
• Approximately 10 mL of venous blood will be collected prior to study vaccination for future 
research from subjects who consent to collection of serum for future use, either by signing an 
ICF 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 ICF allows the option to 
choose that option. 
• Subjects will then receive a single dose of study vaccine via IM injection into the deltoid 
muscle of the preferred arm. The site of injection (right or left arm) and time of 
administration will be recorded on the appropriate data collection form. Subjects will be 
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vaccination site will be examined, post-administration reactogenicity assessments will be 
performed, and any AE/SAEs will be recorded on the appropriate data collection form prior 
to discharge from the clinic. 
• Subjects will be provided with a Memory Aid and other study-related materials to record 
daily oral temperature, solicited injection site and systemic reactions, any unsolicited AEs, 
and concomitant medications. Subjects will be encouraged to take their oral temperature 
around the same time each day. Subjects must not eat or drink anything hot or cold, or smoke 
within 10 minutes prior to taking oral temperature. Subjects will be instructed on how to use 
their Memory Aid and how to measure and record AEs prior to discharge from the clinic. 
Subjects will be instructed to notify the study center if they develop any severe reactions 
after the first study vaccination. If the site principal investigator or appropriate sub-
investigator deems the reaction severe enough, further instructions will be given to the 
subject on the proper course of action, including a return to the clinic for immediate 
evaluation if appropriate. 
 
Planned Study Visits 
 
Follow-up  
Follow-up visits are scheduled in reference to study vaccination dates as indicated for each visit 
window. 
Visit 02, Day 4, Memory Aid Review, Phone Call 
(Window: Day 4±1 days post first study vaccination) 
Study personnel will contact subjects by phone to solicit any 
AEs/SAEs/MAAEs/NOCMCs/PIMMCs, medical history, and concomitant medication 
information and review information on their Memory Aid. Based on the information, subjects 
may be asked to return to the clinic for evaluation. 
Visit 03, Day 8, Clinic Visit 
(Window: Day 8+2 days post first study vaccination) 
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects and any changes since the previous clinic visit or contact will be noted. 
• Memory Aid information will be reviewed with subjects. 


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• 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). 
• All AE/SAEs/MAAEs/NOCMCs/PIMMCs will be recorded on the appropriate data 
collection form.  
• A targeted physical examination, including an assessment for signs suggestive of PIMMCs, 
may be performed, if indicated based on review of interim medical history, by a study 
clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as the site PI 
or sub-investigator. 
• The first study vaccination site will be examined. 
• Approximately 10 mL of venous blood will be collected for clinical safety labs (WBC, Hgb, 
PLT, ALT, T. Bili, Cr), and performed by the central (clinical) laboratory.  
• Approximately 10 mL of venous blood will be collected for serum antibody assays. 
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent to collection of serum for future use either by signing an ICF that includes 
collection of future use samples as a condition of study participation or by indicating that 
they can opt in to sample collection for future use if the ICF allows the option to choose that 
option. 
Visit 04, Day 22, Second Study Vaccination (Dose 2), Clinic Visit 
(Window: Day 22+7 days post first study vaccination) 
• Eligibility criteria will be reviewed with subjects prior to the second study vaccination to 
ensure continued eligibility. 
• For a subject to receive the second study vaccination, refer to section 8.6.2 for second 
vaccination 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 second study vaccination and any changes since the previous clinic visit 
or contact will be noted. 


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


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condition of study participation or by indicating that they can opt in to sample collection for 
future use if the ICF allows the option to choose that option. 
• Subjects will then receive a single dose of study vaccine via IM injection into the deltoid 
muscle of the preferred arm. The second study vaccination may be given in the same 
preferred arm as long as there is no interference with the reactogenicity assessment. The site 
of injection (right or left arm) and time of administration will be recorded on the appropriate 
data collection form. Subjects will be observed in the clinic for at least 20 minutes after the 
second study vaccination. The second study vaccination site will be examined, post-
administration reactogenicity assessments will be performed, and any AE/SAEs will be 
recorded on the appropriate data collection form prior to discharge from the clinic. 
• Subjects will be provided with a Memory Aid and other study-related materials to record 
daily oral temperature, solicited injection site and systemic reactions, any unsolicited AEs, 
and concomitant medications. Subjects will be encouraged to take their oral temperature 
around the same time each day. Subjects must not eat or drink anything hot or cold, or smoke 
within 10 minutes prior to taking oral temperature. Subjects will be instructed on how to use 
their Memory Aid and how to measure and record AEs prior to discharge from the clinic. 
Subjects will be instructed to notify the study center if they develop any severe reactions 
after the second study vaccination. If the site PI or appropriate sub-investigator deems the 
reaction severe enough, further instructions will be given to the subject on the proper course 
of action, including a return to the clinic for immediate evaluation if appropriate. 
Visit 05, Day 25, Memory Aid Review, Phone Call 
(Window: Day 4 ±1 days post second study vaccination) 
Study personnel will contact subjects by phone to solicit any AE/SAE, medical history, and 
concomitant medication information (including solicitation for receipt of any non-study 
influenza vaccines), including those that are experimental, what type (inactivated or live 
attenuated), what subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be 
recorded on the appropriate DCF, if known and not previously collected) and review information 
on their Memory Aid. Based on the information, subjects may be asked to return to the clinic for 
evaluation. Note: For subjects who are discontinued from the receipt of the second study 
vaccination, AEs will be limited to SAEs, MAAEs, including NOCMCs, and PIMMCs. 
Visit 06, Day 29, Clinic Visit 
(Window: Day 8+2 days post second study vaccination) 
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects and any changes since the previous clinic visit or contact will be noted. 


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• 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). 
• All AE/SAEs will be recorded on the appropriate data collection form. Note: for subjects 
who discontinued from the receipt of the second study vaccination, AEs will be limited to 
SAEs, MAAEs, including NOCMCs, and PIMMCs. 
• A targeted physical examination, including an assessment for signs suggestive of PIMMCs, 
may be performed, if indicated based on review of interim medical history, by a study 
clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as the site PI 
or sub-investigator. 
• The second study vaccination site will be examined. 
• Approximately 10 mL of venous blood will be collected for clinical safety labs (WBC, Hgb, 
PLT, ALT, T. Bili, and Cr), and performed by the central (clinical) laboratory.  
• Approximately 10 mL of venous blood will be collected for serum antibody assays. 
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent to collection of serum for future use either by signing an ICF that includes 
collection of future use samples as a condition of study participation or by indicating that 
they can opt in to sample collection for future use if the ICF allows the option to choose that 
option. 
Visit 07, Day 43, Clinic Visit 
(Window: Day 22+7 days post second study vaccination) 
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic diseases, and symptoms suggestive of PIMMCs, will be obtained by interview of 
subjects and any changes since the previous clinic visit or contact will be noted. 
• 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). 


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• All AE/SAEs will be recorded on the appropriate data collection form. Note: for subjects 
who discontinued from the receipt of the second study vaccination, AEs will be limited to 
SAEs, MAAEs, including NOCMCs, and PIMMCs. 
• A targeted physical examination, including an assessment for signs suggestive of PIMMCs, 
may be performed, if indicated based on review of interim medical history, by a study 
clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as the site PI 
or sub-investigator. 
• Approximately 10 mL of venous blood will be collected for serum antibody assays.  
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent to collection of serum for future use either by signing an ICF that includes 
collection of future use samples as a condition of study participation or by indicating that 
they can opt in to sample collection for future use if the ICF allows the option to choose that 
option. 
Visit 08, Day 82, Safety Follow-up, Phone Call 
(Window: Day 61±7 days post second study vaccination) 
Subjects will be contacted by phone to query for safety events and solicitation for receipt of all 
concomitant medications (including any solicitation for receipt of any non-study influenza 
vaccines), including those that are experimental, what type (inactivated or live attenuated), what 
subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be recorded on the 
appropriate DCF, if known and not previously collected. Adverse events limited to MAAEs 
including NOCMCs, PIMMCs, and SAEs that have occurred since the previous clinic visit or 
contact will be solicited. Based on the information, subjects may be asked to return to the clinic 
for evaluation. 
Visit 09, Day 142, Safety Follow-up, Phone Call 
(Window: Day 121±14 days post second study vaccination) 
Subjects will be contacted by phone to query for safety events and solicitation for receipt of all 
concomitant medications (including any solicitation for receipt of any non-study influenza 
vaccines), including those that are experimental, what type (inactivated or live attenuated), what 
subtype (e.g., A/H3, A/H5, A/H9) and approximate date of vaccination will be recorded on the 
appropriate DCF, if known and not previously collected. Adverse events limited to MAAEs 
including NOCMCs, PIMMCs, and SAEs that have occurred since the previous clinic visit or 
contact will be solicited. Based on the information, subjects may be asked to return to the clinic 
for evaluation. 


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Visit 10, Day 202, Safety Follow-up, Clinic Visit 
(Window: Day 181±14 days post second study vaccination) 
• Interim medical history, including an assessment for new medical conditions, stability of 
chronic medical diseases, and symptoms suggestive of PIMMCs, will be obtained by 
interview of subjects and any changes since the previous clinic visit or contact will be noted. 
• 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). 
• Adverse events limited to MAAEs including NOCMCs, PIMMCs, and SAEs that have 
occurred since the previous clinic visit or contact will be solicited.  
• A targeted physical examination, including an assessment for signs suggestive of PIMMCs, 
may be performed, if indicated based on review of interim medical history, by a study 
clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as the site PI 
or sub-investigator. 
• Approximately 10 mL of venous blood will be collected for serum antibody assays.  
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent to collection of serum for future use either by signing an ICF that includes 
collection of future use samples as a condition of study participation or by indicating that 
they can opt in to sample collection for future use if the ICF allows the option to choose that 
option. 
 
Final Study Visit, Visit 11, Day 387, Safety Follow-up, Phone Call 
(Window: Day 366±14 days post second study vaccination) 
Subjects will be contacted by phone to query for safety events.  AEs limited to MAAEs 
including NOCMCs, and PIMMCS, and SAEs that have occurred since the previous clinic visit 
or contact will be solicited.  Based on the information, subjects may be asked to return to the 
clinic for evaluation. 
 
Early Termination Visit (if needed) 
The following activities will be performed at the early termination visit on subjects who 
withdraw, or are withdrawn or terminated from this trial: 


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• Interim medical history, including an assessment for new medical conditions and symptoms 
suggestive of PIMMCs, will be obtained by interview of subjects and any changes since the 
previous clinic visit or contact will be noted. 
• Memory Aid information will be reviewed with subjects (if within 7 days after the last study 
vaccination). 
• All concomitant medications will be recorded on the appropriate data collection form (if 
within 180 days after the last study vaccination, 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). Receipt of any non-study influenza vaccine will be recorded if within 180 days 
after the last study vaccination. 
• Unsolicited non-serious AEs will be documented and reported from the time of each study 
vaccination through approximately 21 days after each study vaccination.   SAEs, MAAEs, 
including NOCMCs, and PIMMCs will be documented and reported from the time of the 
first study vaccination through approximately  12 months after last study vaccination).  
• Vital signs, including oral temperature, pulse, and blood pressure, may be obtained if 
indicated. Subjects must not eat or drink anything hot or cold, or smoke within 10 minutes 
prior to taking oral temperature. 
• A targeted physical examination, including an assessment for signs suggestive of PIMMCs, 
may be performed, if indicated based on review of interim medical history, by a study 
clinician licensed to make medical diagnoses and listed on the Form FDA 1572 as the site PI 
or sub-investigator. 
• The study vaccination site will be examined (if within 7 days after the last study vaccination). 
• Post-administration reactogenicity assessments will be performed (if within 7 days after the 
last study vaccination). 
• Approximately 10 mL of venous blood will be collected for serum antibody assays (if within 
21 days after the last study vaccination). 
• Approximately 10 mL of venous blood will be collected for clinical safety labs (WBC, Hgb, 
PLT, ALT, T. Bili, and Cr), and performed by the central (clinical) laboratory if done within 
7 days after the last study vaccination.  


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• Approximately 10 mL of venous blood will be collected for future research (if within 21 days 
after the last study vaccination) from subjects who consent to collection of serum for future 
use either by signing an ICF that includes collection of future use samples as a condition of 
study participation or by indicating that they can opt in to sample collection for future use if 
the ICF allows the option to choose that option. 
6.5 
Unscheduled Visit (if needed) 
Unscheduled visits may occur at any time during this trial. Any of the following activities may 
be performed: 
• Interim medical history, including an assessment for new medical conditions and symptoms 
suggestive of PIMMCs, will be obtained by interview of subjects and any changes since the 
previous clinic visit or contact will be noted (if indicated). 
• Memory Aid information will be reviewed with subjects (if within 7 days after the last study 
vaccination). 
• All concomitant medications will be recorded on the appropriate data collection form (if 
within 180 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 study vaccination. 
• Unsolicited non-serious AEs will be documented and reported from the time of each study 
vaccination through approximately 21 days after each study vaccination. SAEs, MAAEs, 
including NOCMCs, and PIMMCs will be documented and reported from the time of the 
first study vaccination through approximately  12 months after the last study vaccination. 
• 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 PI 
or sub-investigator. 
• The study vaccination site will be examined (if within 7 days after the last study vaccination). 


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• Post-administration reactogenicity assessments will be performed (if within 7 days after the 
last study vaccination). 
• Approximately 10 mL of venous blood will be collected for serum antibody assays (if within 
21 days after the last study vaccination).  
• Approximately 10 mL of venous blood will be collected for clinical safety labs (WBC, Hgb, 
PLT, ALT, T. Bili, and Cr), and performed by the central (clinical) laboratory if indicated.  
• Approximately 10 mL of venous blood will be collected for future research from subjects 
who consent to collection of serum for future use (if within 21 days after the last study 
vaccination) either by signing an ICF that includes collection of future use samples as a 
condition of study participation or by indicating that they can opt in to sample collection for 
future use if the ICF allows the option to choose that option. 
6.6 
Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol, or protocol-specific 
MOP requirements.  The noncompliance may be either on the part of the subject, the site PI, or 
the site 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 PI and personnel to use continuous vigilance to identify and 
report deviations within five working days of identification of the protocol deviations, or within 
five working days of the scheduled protocol-required activity.  All deviations must be promptly 
reported to DMID per the SDCC protocol deviation reporting procedures. 
All deviations, as defined above, must be addressed in study subject data collection forms.  A 
completed copy of the DMID Protocol Deviation Form must be maintained in the regulatory file, 
as well as the subject’s chart.  Protocol deviations must be sent to the local IRB/IEC per their 
guidelines.  The site PI and personnel are responsible for knowing and adhering to their IRB 
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7 
DESCRIPTION OF CLINICAL AND LABORATORY 
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. 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 7.1.1. 
At the screening visit (optional) or the baseline visit (Day 1) a physical examination will be 
performed on all subjects to include the following organs and organ systems: including skin, 
head and neck, lungs, heart, liver, spleen, extremities, lymph nodes, abdomen, general 
appearance, musculoskeletal, and nervous system, by a study clinician licensed to make medical 
diagnoses and listed on the Form FDA 1572 as the site PI or sub-investigator. At follow-up visits 
after the first study vaccination, a targeted physical examination may be performed, if indicated 
based on the subject’s interim medical history, by a study clinician licensed to make medical 
diagnoses and listed on the Form FDA 1572 as the site PI or sub-investigator. Targeted physical 
examinations should also include an assessment for signs suggestive of PIMMCs. 
Vital signs (oral temperature, pulse, and blood pressure) will be collected at the screening visit 
(optional) and prior to each study vaccination (Days 1 and 22). Vital signs assessed on Day 1 
prior to the first study vaccination will be considered as baseline. Subjects must not eat or drink 
anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
Height and weight will be collected at the screening visit (optional) or on Day 1 prior to the first 
study vaccination for the calculation of 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, ecchymosis, erythema, induration/ 
swelling, pain, and tenderness as well as systemic reactions including fever, feverishness, 


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fatigue, malaise, myalgia, arthralgia, headache, and nausea. Pre-administration reactogenicity 
assessments will be performed prior to each study vaccination to establish baseline, then the 
study vaccination will be given. 
Subjects will be observed in the clinic for at least 20 minutes after each study vaccination. The 
study vaccination site will be examined, post-administration reactogenicity assessments will be 
performed, and any AE/SAEs will be recorded on the appropriate data collection form prior to 
discharge from the clinic. The study vaccination site will also be examined approximately 7 days 
after each study vaccination. 
All subjects will complete a subject Memory Aid from the time of each study vaccination 
through 7 days after each study vaccination. Subject Memory Aids will be reviewed with the 
subjects for AEs (solicited injection site and systemic reactions and unsolicited AEs) 
approximately 3 and 7 days after each study vaccination via phone call (Day 4) and clinical visit 
(Day 8). 
 
Assessment of Concomitant Medications/Treatments other than Study Product 
Administration of any medications, therapies, or vaccines will be recorded on the appropriate 
data collection form. Concomitant medications will include all current medications and 
medications taken in the 60 days prior to signing the ICF through approximately 180 days after 
the last study vaccination or early termination (if prior to 180 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 180 days after the last study vaccination. Prescription and over-the-counter drugs 
will be included as well as herbals, vitamins, and supplements. In addition, receipt of non-study 
influenza vaccines will be solicited through approximately 180 days after the last study 
vaccination, and reported in the eCRF. Use of a new medication should prompt evaluation for 
the occurrence of any MAAE, including a new diagnosis of chronic medical disease or condition. 
Medications that might interfere with the evaluation of the investigational product(s) should not 
be used during the trial-reporting period (approximately 12 months after the last study 
vaccination) unless clinically indicated as part of the subject’s health care. Medications in this 
category include the prohibited medications per the Subject Exclusion Criteria (see Section 
5.1.2). In addition, the site PI or appropriate sub-investigator may identify other medications that 
should not be used due to a risk to subject safety or assessment of reactogenicity and 
immunogenicity. 


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7.2 
Laboratory Evaluations 
7.2.1 
Clinical Laboratory Evaluations 
Serum or urine pregnancy tests will be performed.    Serum or urine pregnancy tests will be 
performed locally by site laboratory.  Pregnancy testing will be done 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.  
Clinical safety laboratory parameters (WBC, Hgb, PLT, ALT, T. Bili, and Cr) will be collected 
from each subject prior to each study vaccination and approximately 7 days after each study 
vaccination. These evaluations will be performed by the central (clinical) laboratory. Venous 
blood samples (approximately 10 mL) will be collected for these safety labs. The results from the 
clinical safety laboratory parameters collected on Day 1 will not be available or reviewed prior to 
study vaccination, and will serve as a safety baseline assessment only. 
The volume of venous blood to be collected for the clinical safety laboratory evaluations is 
presented in Table 2. 
7.2.2 
Research Assays  
Immunogenicity 
Assays to determine serum levels of HAI and Neut antibodies will be performed at Southern 
Research. Venous blood samples (approximately 10 mL) for antibody assays will be collected 
from each subject immediately prior to each study vaccination (Day 1 and approximately Day 
22) and, approximately 7 days after each study vaccination (approximately Day 8 and Day 29), 
and approximately 21 days and 180 days after the second study vaccination (approximately Days 
43 and 202). Subjects who withdraw early will have HAI and Neut antibody assays run on 
available sera. 
Venous blood samples (10 mL) will also be collected for future use at the same time points. Sites 
may elect to allow subjects to consent to study participation but to have the option to opt in for 
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 option.  
The assays for determination of the NA content and antibodies to the NA are under development. 
If successful, the correlation of NA content in the 2017 H7N9 IIV with elicited N9 NA-specific 
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7.2.2.2 
Laboratory Specimen Shipment 
Specimen shipment will occur at intervals during the course of this trial following all applicable 
International Air Transport Association (IATA) requirements and according to the specifics for 
storage temperature and documentation as detailed in the central (clinical) laboratory manual and 
protocol-specific MOP as appropriate. 
Specimens for safety laboratory evaluations will be shipped from the participating VTEU sites to 
the central (clinical) laboratory. 
Specimens for HAI and Neut antibody assays will be shipped from the participating VTEU sites 
to the DMID CMS, and then provided by the DMID CMS to Southern Research in a blinded 
manner. 
Specimens for the NA antibody assays will be shipped from the participating VTEU sites to the 
DMID CMS, and then provided by the DMID CMS to the NA antibody assay laboratory once it 
has been identified. 
Further instructions for specimen shipment are included in the central (clinical) laboratory 
manual and protocol-specific MOP, as appropriate. 
 
 


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8 
ASSESSMENT OF SAFETY 
8.1 
Assessing and Recording Safety Parameters 
Safety will be assessed by the frequency and severity of: 
1. SAEs occurring from the time of the first study vaccination through approximately 12 
months after the last study vaccination. 
2. Solicited AEs – reactogenicity events occurring from the time of each study vaccination 
through 7 days after each study vaccination: 
a) Injection site reactions including pruritus, ecchymosis, erythema, induration/swelling, 
pain, and tenderness. 
b) Systemic reactions including fever, feverishness, fatigue, malaise, myalgia, arthralgia, 
headache, and nausea. 
3. Clinical safety laboratory AEs occurring from the time of each study vaccination through 
approximately 7 days after each study vaccination.  Parameters to be evaluated include 
WBC, Hgb, PLT, ALT, T. Bili, and 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. 
8.1.1 
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. FDA defines an AE as any untoward medical occurrence 
associated with the use of a drug in humans, whether or not considered drug related. 
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a medicinal (investigational) 
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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All AEs, including solicited local (injection site) and systemic (subjective and quantitative) 
reactions, will be captured on the appropriate data collection form and eCRF. Information to be 
collected for AEs includes event description, date of onset, assessment of severity, relationship to 
study product and alternate etiology (assessed only by those with the training and authority to 
make a diagnosis and listed on the Form FDA 1572 as an investigator), date of resolution, 
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 unsolicited AE. However, if the severity or frequency of any 
pre-existing medical condition increases, it will be recorded as an unsolicited AE. 
If an event meets both the criteria of a study endpoint and an adverse event, the event will be 
reported either as a study endpoint or as an adverse event (not both). 
8.1.1.1 
Adverse Events Grading 
All AEs (laboratory and clinical symptoms) will be graded for severity and assessed for 
relationship to study product (see definitions). AEs characterized as intermittent require 
documentation of onset and duration of each episode.  The start and stop date of each reported 
AE will be recorded on the appropriate data collection form and eCRF. Changes in the severity 
of an AE will be documented to allow an assessment of the duration of the event at each level of 
intensity. 
Severity of Event: 
AEs will be assessed by the investigator using a protocol-defined grading system (toxicity table). 
For events not included in the protocol-defined grading system, the following guidelines will be 
used to quantify severity: 
• 
Mild (Grade 1): Events require minimal or no treatment and do not interfere with the 
subject’s daily activities. 
• 
Moderate (Grade 2): Events result in a low level of inconvenience or concern with 
therapeutic measures. Moderate events may cause some interference with functioning and 
daily activities. 
• 
Severe (Grade 3): Events interrupt the subject’s daily activities and may require systemic 
drug therapy or other treatment. Severe events are usually incapacitating. 


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Changes in the severity of an AE should be documented to allow for assessment of the duration 
of the event at each level of intensity to be performed.  AEs characterized as intermittent require 
documentation of onset and duration of each episode. 
Relationship to Study Product: The assessment of the relationship of an AE to the 
administration of study product is made only by those with the training and authority to make a 
diagnosis and listed on the Form FDA 1572 as an investigator based on all available information 
at the time of the completion of the eCRF.  Whether the AE is related or not, 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.  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. 
8.1.2 
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: 
Table 3: Injection Site Reactogenicity Grading 
Injection Site Reaction 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Pain – experienced 
without touching the 
injection site 
(spontaneous 
discomfort) 
Subject is aware of pain, 
but it does not interfere 
with daily activity, and if 
pain medication is used, it 
is Over the Counter 
(OTC) and used for less 
than 24 hours 
Subject is aware of pain; 
there is interference with 
daily activity or OTC 
pain medication is used 
for more than 24 hours 
Subject is aware of pain, 
and it prevents daily 
activity or pain requires 
prescription medication 
Tenderness – hurts only 
when injection site is 
touched or the arm is 
moved 
The area immediately 
surrounding the injection 
site hurts only when 
touched or with arm 
motion, and it does not 
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 


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Injection Site Reaction 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
interfere with daily 
activity 
Pruritus (Itching) 
Does not interfere with 
daily activity 
Interferes with daily 
activity 
Prevents daily activity 
Ecchymosis 
Does not interfere with 
daily activity 
Interferes with daily 
activity 
Prevents daily activity 
Erythema 
Does not interfere with 
daily activity 
Interferes with daily 
activity 
Prevents daily activity 
Induration/Swelling 
Does not interfere with 
daily activity 
Interferes with daily 
activity 
Prevents daily activity 
Ecchymosis, erythema, and induration/swelling as analyzed by measurement will be graded as 
follows: 
Table 4: Injection Site Reactogenicity Measurements 
Injection Site Reaction 
Small 
Medium 
Large 
Ecchymosis* 
<20 mm 
20 mm – 50 mm 
>50 mm 
Erythema* 
<20 mm 
20 mm – 50 mm 
>50 mm 
Induration/Swelling* 
<20 mm 
20 mm – 50 mm 
>50 mm 
* Will not be used as halting criteria. 
Table 5: Subjective Systemic Reactogenicity Grading 
Systemic (Subjective) 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Feverishness  
No interference with 
daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Fatigue  
No interference with 
daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Malaise  
No interference with 
daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Myalgia* 
No interference with 
daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Arthralgia * 
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) 
Headache 
No interference with 
daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
Nausea 
No interference with 
daily activity 
Some interference with 
daily activity 
Significant interference, 
prevents daily activity 
* Not at injection site. 
Oral temperature# will be graded as follows: 
Table 6: 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. 
Table 7: Pulse and Blood Pressure Grading for Subjects 18-64 years of age 
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. 
8.1.3 
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: 


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• 
Death, 
• 
A life-threatening AE*, 
• 
Inpatient hospitalization or prolongation of existing hospitalization, 
• 
A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions, or 
• 
A congenital anomaly/birth defect. 
• 
Important medical events that may not result in death, be life-threatening, or require 
hospitalizations may be considered serious when, based upon appropriate medical 
judgment they may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse. 
* Life-threatening AE. An AE is considered “life-threatening” if, in the view of either the site 
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. 
• 
Recorded on the appropriate SAE data collection form and eCRF. 
• 
Followed through resolution. 
• 
Reviewed and evaluated by an Independent Safety Monitor (ISM) (as deemed necessary), 
the SMC (periodic review unless related), DMID, and the IRB. 
At any time after protocol follow up period or completion of this study, 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. 


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8.2 
Specifications of Safety Parameters 
Safety will be assessed by the frequency and severity of: 
8.2.1 
Solicited Events 
Solicited events are AEs that are common and known to occur following administration of study 
product. 
8.2.2 
Unsolicited Events 
Unsolicited events are any other AEs that occur following administration of study product. 
8.2.3 
New Onset Chronic Medical Conditions (NOCMCs) 
NOCMCs are defined as any new ICD-10 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. 
8.2.4 
Medically Attended Adverse Events (MAAEs) 
For each unsolicited AE experienced, the subject will be asked if he/she had received medical 
attention, defined as hospitalization, an emergency room visit, or an otherwise unscheduled visit 
to or from medical personnel for any reason. AEs characterized by such unscheduled medical 
care will be designated as MAAEs. 
8.2.5 
Potentially Immune Mediated Medical Conditions (PIMMCs) 
PIMMCs constitute a group of AEs that includes diseases which are clearly autoimmune in 
etiology and other inflammatory and/or neurologic disorders which may or may not have 
autoimmune etiologies. PIMMCs currently in effect are presented in APPENDIX B. LIST OF 
POTENTIALLY IMMUNE MEDIATED MEDICAL CONDITIONS  
8.3 
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. 


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Unsolicited non-serious AEs will be documented and reported from the time of each study 
vaccination through approximately 21 days after each study vaccination. 
SAEs, MAAEs, including NOCMCs, and PIMMCs will be documented and reported from the 
time of the first study vaccination through approximately 12 months after the last study 
vaccination. 
8.3.1 
Reporting Serious Adverse Events 
SAEs will be followed until resolution even if this extends beyond the study-reporting period.  
Resolution of an AE is defined as the return to pretreatment status or stabilization of the 
condition with the expectation that it will remain chronic. 
Any AE that meets a protocol-defined serious criterion must be submitted immediately 
(within 24 hours of site awareness) on an SAE form to the DMID Pharmacovigilance 
Group at the following address: 
DMID Pharmacovigilance Group 
Clinical Research Operations and Management Support (CROMS) 
6500 Rock Spring Dr. Suite 650 
Bethesda, MD 20817, USA 
 
 
 
 
In addition to the SAE form, selected SAE data fields must also be entered into the DCC system 
(for example AdvantageEDC). 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. 
At any time after completion of this trial, if the site PI or appropriate sub-investigator becomes 
aware of an SAE that is suspected to be related to study product, the site PI or appropriate sub-
investigator will report the event to the DMID Pharmacovigilance Group. 


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8.3.2 
Regulatory Reporting for Studies Conducted Under DMID Sponsored IND 
Following notification from the investigator, DMID, the Investigational New Drug (IND) 
sponsor, will report any suspected adverse reaction that is both serious and unexpected. DMID 
will report an AE as a suspected adverse reaction only if there is evidence to suggest a causal 
relationship between the drug and the AE. DMID will notify FDA and all participating site 
investigators (i.e., all investigators to whom the sponsor is providing drug under its IND(s) or 
under any PI’s IND(s)) in an IND safety report of potential serious risks from clinical trials or 
any other source, as soon as possible, but in no case later than 15 calendar days after the sponsor 
determines that the information qualifies for reporting as specified in 21 CFR Part 312.32. DMID 
will also notify 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. 
8.3.3 
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. 
8.3.4 
Disclosure of Study Related Information 
Subjects can choose to receive written disclosure of their treatment assignment after the database 
has been locked.  
8.4 
Type and Duration of Follow-up of Subjects after Adverse Events 
AEs will be collected, assessed, and followed through resolution from the time of each study 
vaccination through approximately 21 days after each study vaccination. 


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SAEs, MAAEs, including NOCMCs, and PIMMCs will be collected, assessed, and followed 
from the time of the first study vaccination through resolution even if this extends beyond the 
trial-reporting period (approximately 12 months after the last study vaccination). 
Resolution of an AE/SAE is defined as the return to pretreatment status or stabilization of the 
condition with the expectation that it will remain chronic. 
Follow-up procedures, evaluations, and outcomes will be recorded on the appropriate data 
collection form. 
8.5 
Procedures to be Followed in the Event of Abnormal Laboratory 
Test Values or Abnormal Clinical Findings 
The site PI or appropriate sub-investigator is responsible for recording all AE/SAEs that are 
observed or reported during this trial, regardless of 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. 
Clinical safety laboratory results# will be graded as follows: 
Clinical Safety Laboratory Adverse Event Grading
# 
Hematology 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
WBC 103/µL (Decrease) 
2.5 – 3.9 
1.5 – 2.4 
<1.5 
WBC 103/µL (Increase) 
10.6 – 15.0 
15.1 – 20.0 
>20.0 
Hgb g/dL (Decrease) (Female) 
10.1 – 11.4 
8.5 – 10 
<8.5 
Hgb g/dL (Decrease) (Male) 
11.0 – 12.4 
9.5 – 10.9 
<9.5 
Platelets 103/µL (Decrease) 
125 – 139 
100 – 124 
<100 
Platelets 103/µL (Increase) 
416 – 550 
551– 750 
>750 
 
 
 
 
Chemistry 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
ALT IU/L (Increase) (Female) 
44 – 100 
101 – 200 
>200 
ALT IU/L (Increase) (Male) 
61 – 138 
139 – 275 
>275 
Total Bilirubin mg/dL (Increase) – 
when accompanied by any increase in 
ALT 
1.30 – 1.59 
1.60 – 1.80 
>1.80 


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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. 
 
 
8.6 
Halting Rules 
8.6.1 
Study Halting Criteria 
Further enrollment and study vaccinations will be halted for DSMB review/recommendation if 
any of the following are reported: 
• Any subject experiences ulceration, abscess, or necrosis at the injection site related to study 
product administration. 
• Any 2 or more subjects experience laryngospasm, bronchospasm, or anaphylaxis within 1 
day after administration of study product that is considered related to study product. 
• Three or more subjects experience generalized urticaria (defined as occurring at more than 
two body parts) within 3 days after administration of study product that is considered related 
to study product. 
• Any subject experiences a study vaccine-related SAE from the time of the first study 
vaccination through the subject’s last study visit. 
• Any subject experiences acute weakness of limbs and/or cranial nerve innervated muscles 
(description of potential signal of GBS) after administration of study product. 
• Any subject develops a PIMMC after administration of study product. 
This trial will also be halted for DSMB review/recommendation if, within 7 days after 
administration of either study vaccination, any of the following occurs within the MF59®-
adjuvanted treatment arms or within the one unadjuvanted treatment arm.   
• 7% or more of subjects (with a minimum of 3 subjects) who received at least one dose of 
study vaccine to date, cumulative to both vaccine administrations, across all groups, 
experience the same severe (Grade 3) study vaccine-related injection site reaction. 


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Ecchymosis, erythema, and induration/swelling will also be measured in mm but size will not 
be used as halting criteria.  
• 7% or more of subjects (with a minimum of 3 subjects) who received at least one dose of 
study vaccine to date, cumulative to both vaccine administrations, across all groups, 
experience the same severe (Grade 3) study vaccine-related subjective systemic reaction, for 
which the severity (grade) is corroborated by study personnel. 
• 7% or more of subjects (with a minimum of 3 subjects) who received at least one dose of 
study vaccine to date, cumulative to both vaccine administrations, across all groups, 
experience the same severe (Grade 3) study vaccine-related quantitative systemic reaction. 
• 7% or more of subjects (with a minimum of 3 subjects) who received at least one dose of 
study vaccine to date, cumulative to both vaccine administrations, across all groups, 
experience the same severe (Grade 3) study vaccine-related clinical safety laboratory AE. 
Grading scales for solicited injection site and systemic (subjective and quantitative) reactions are 
included in Section 8.1.2. 
Grading scales for clinical safety laboratory AEs are included in Section 8.5. 
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. 
8.6.2 
Individual Halting Criteria 
The second study vaccination will not be administered to a subject if any of the following criteria 
are met: 
•  Subject meets any criteria in Section 5.2.1, Withdrawal from the Study or Discontinuation of 
the Study Product.  
• Presence of signs or symptoms that could confound or confuse assessment of study vaccine 
reactogenicity. For subjects with injection site or systemic signs or symptoms, or with an 
acute illness, including an oral temperature greater than or equal to 100°F, the second study 


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vaccination should be postponed/deferred until signs, symptoms, or acute illness have 
resolved, or are improving as further specified below, and if within the acceptable protocol-
specified window for that visit (Day 22+7) (note:  Grade 1 vaccine related solicited AE are 
permitted, see below). No exceptions to the protocol-specified window will be made. Note 
for afebrile, acute illness only: If a subject is afebrile, his/her acute illness is nearly resolved 
with only minor residual symptoms remaining, this occurs within the acceptable protocol-
specified window for that visit (Day 22+7), and, in the opinion of the site PI or appropriate 
sub-investigator, the residual symptoms will not interfere with the ability to assess safety 
parameters as required by the protocol, the subject may receive the second study vaccination 
without further approval from the DMID Medical Officer. No exceptions to the protocol-
specified window will be made.  
• Grade 3 solicited or unsolicited AE that is ongoing, whether or not it is improved or 
resolving.  
• Any unresolved or continuing Grade 2 AE that has not decreased in severity to Grade 1 or 
less.   
• An unresolved or continuing Grade 1 AE is permissible following the documented 
determination by the site PI or appropriate sub-investigator, that it would not render study 
vaccination unsafe or interfere with the evaluation of responses. 
• Grade 3 solicited or unsolicited AE that occurs without alternative etiology in the 8 days 
following the first study vaccination. 
• Grade 3 clinical safety laboratory value (according to the toxicity table, Section 8.5) that does 
not decrease to Grade 2 or less prior to the second study vaccination.  Any clinical safety 
laboratory parameter may be re-evaluated only once at the central (clinical) laboratory in 
order to assess eligibility prior to the second study vaccination.  If the clinical safety 
laboratory value decreases to Grade 2 or less, the subject may receive the second study 
vaccination.  The second study vaccination should be scheduled to occur within the 
acceptable protocol-specific window for that visit (Day 22+7 days post first study 
vaccination).  No exceptions to the protocol-specified window will be made. 
• Subject no longer meets eligibility criteria the Subject Exclusion Criteria (see Section 5.1.2). 
Note: exception for Medication changes described in Section 5.2.1.  
• Hospitalization that occurs before administration of the second study vaccination.  


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8.7 
Safety Oversight 
8.7.1 
Independent Safety Monitor (ISM) 
The ISM is a physician with relevant expertise whose primary responsibility is to provide to 
DMID an independent safety assessment in a timely fashion. For this trial an ISM is not required. 
However, at each participating VTEU site, upon DMID Medical Monitor request, the PI will 
identify a physician with relevant expertise, to act as a Secondary Medical Assessor (SMA).  The 
SMA will examine a subject and/or medical records and provide a medical assessment (or 
second medical opinion) to the DMID of the safety event in question.  The PI will send to the 
DMID, MM, a summary of the event and include the PI and SMA assessments. 
Note: In case that DMID has requested this type of evaluation multiple times, DMID may 
request the site(s) identify an ISM to assist DMID with safety oversight. 
8.7.2 
Data and Safety Monitoring Board (DSMB) 
Safety oversight will be conducted by a DSMB that is an independent group of experts that 
monitors subject safety and advises DMID. The DSMB members will be separate and 
independent of study personnel participating in this trial and should not have scientific, financial 
or other conflict of interest related to this trial. The DSMB will consist of members with 
appropriate expertise to contribute to the interpretation of the data from this trial. The DSMB 
will operate under the rules of a DMID-approved charter that will be written at the organizational 
meeting of the DSMB. Procedures for DSMB reviews/meetings will be defined in the charter. 
Reports may include enrollment and demographic information, medical history, concomitant 
medications, physical assessments, clinical laboratory values, dosing compliance, and solicited 
and unsolicited AE/SAEs, HAI and Neut antibody assay results. The DSMB will review SAEs 
on a regular basis and ad hoc during this trial. The DMID Medical Monitor and the ISM (as 
deemed necessary) will be responsible for reviewing SAEs in real time.  
The DSMB will conduct the following reviews: 
• Bi-monthly (every two months) safety data reviews (including monthly safety data and 
cumulative safety data) until the last subject completes the visit that occurs approximately 21 
days after the last study vaccination.  
• Data review 9 days after all subjects have received Dose 2 (complete study visit number 
V06). This review may be conducted as part of the scheduled monthly reviews. 
• Ad hoc when a halting rule is met or DMID/DSMB chair may convene an ad hoc meeting if 
there are immediate concerns regarding observations during the course of this trial. 


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• 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. 
Additional data may be requested by the DSMB, and interim statistical reports may be generated 
as deemed necessary and appropriate by DMID. The DSMB may receive data in aggregate and 
presented by treatment arm. The DSMB may also be provided with expected and observed rates 
of the expected AEs in an unblinded fashion, and may request the treatment assignment be 
unblinded for an individual subject if required for safety assessment. The DSMB will review 
grouped and unblinded data in the closed session only. As an outcome of each review/meeting, 
the DSMB will make a recommendation as to the advisability of proceeding with study 
vaccinations (as applicable), and to continue, modify, or terminate this trial. 


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9 
HUMAN SUBJECT PROTECTION 
9.1 
Institutional Review Board/Independent Ethics Committee 
Each site PI will obtain IRB approval for this protocol to be conducted at his/her research site(s), 
and send supporting documentation to the DMID before initiating recruitment of subjects.  The 
investigator will submit applicable information to the IRB/IEC on which it relies for the review, 
to conduct the review in accordance with 45 CFR 46, ICH E6 GCP, and as applicable, 21 CFR 
56 (Institutional Review Boards) and 21 CFR 50 (Protection of Human Subjects), other federal, 
state, and local regulations.  The IRB/IEC must be registered with the Office of Human Research 
Protection (OHRP) as applicable to the research.  DMID must receive the documentation that 
verifies IRB/IEC-approval for this protocol, associated ICFs, and upon request any recruitment 
material and handouts or surveys intended for the subjects, prior to recruitment and enrollment of 
subjects. 
Any amendments to the protocol or consent materials will be approved by the IRB/IEC before 
they are implemented.  IRB/IEC review and approval will occur at least annually throughout the 
enrollment and follow-up of subjects, and may cease if annual review is no longer required by 
applicable regulations.  The investigator will notify the IRB/IEC of deviations from the protocol 
and reportable SAEs, as applicable to the IRB/IEC policy. 
Each institution engaged in this research will hold a current Federal Wide Assurance (FWA) 
issued by the OHRP for federally funded research.   
9.2 
Informed Consent Process 
Informed consent is a process that is initiated prior to an individual agreeing to participate in a 
trial and continuing throughout the individual’s trial participation. Before any study procedures 
are performed, informed consent will be obtained from the subject and documented.  Subjects 
will receive a concise and focused presentation of key information about the clinical trial, 
verbally and with a written ICF. The explanation will be organized, and presented in lay 
terminology and language that facilitates understanding why one might or might not want to 
participate. 
An investigator or designee will describe the protocol to potential subjects face-to-face.  The key 
information about the purpose of the study, the procedures and experimental aspects of the study, 
risks and discomforts, any expected benefits to the subject, and alternative treatment will be 
presented first to the subject. 
Subjects will also receive an explanation that the trial involves research, and a detailed summary 
of the proposed study procedures and study interventions/products.  This will include aspects of 


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the trial that are experimental, the probability for random assignment to treatment groups, any 
expected benefits, all possible risks (including a statement that the particular treatment or 
procedure may involve risks to the subject or to the embryo or fetus, if the subject is or may 
become pregnant, that are currently unforeseeable), the expected duration of the subject’s 
participation in the trial, alternative procedures that may be available and the important potential 
benefits and risks of these available alternative procedures.  
Subjects will be informed that they will be notified in a timely manner if information becomes 
available that may be relevant to their willingness to continue participation in the trial. Subjects 
will receive an explanation as to whether any compensation and any medical treatments are 
available if injury occurs, and, if so, what they consist of, or where further information may be 
obtained. Subjects will be informed of the anticipated financial expenses, if any, to the subject 
for participating in the trial, as well as any anticipated prorated payments, if any, to the subject 
for participating in the trial. They will be informed of whom to contact (e.g., the investigator) for 
answers to any questions relating to the research project.  
Information will also include the foreseeable circumstances and/or reasons under which the 
subject’s participation in the trial may be terminated. The subjects will be informed that 
participation is voluntary and that they are free to withdraw from the study for any reason at any 
time without penalty or loss of benefits to which the subject is otherwise entitled.   
The extent of the confidentiality of the subjects’ records will be defined, and subjects will be 
informed that applicable data protection legislation will be followed. Subjects will be informed 
that the monitor(s), auditors(s), IRB, NIAID, and regulatory authority(ies) will be granted direct 
access to the subject’s original medical records for verification of clinical trial procedures and/or 
data without violating the confidentiality of the subject, to the extent permitted by the applicable 
laws and regulations, and that, by signing a written ICF, the subject is authorizing such access.  
 
Subjects will be informed that records identifying the subject will be kept confidential, and, to 
the extent permitted by the applicable laws and/or regulations, will not be made publicly 
available and, if the results of the trial are published, the subject’s identity will remain 
confidential. Subjects will be informed whether private information collected from this research 
and/or specimens will be used for additional research, even if identifiers are removed.   
Subjects will be allowed sufficient time to consider participation in this research trial, 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 will be IRB-approved and subjects will be asked to read and review the consent form. 
Subjects must sign the ICF prior to starting any study procedures being done specifically for this 
trial. 
 


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Once signed, a copy of the ICF will be given to the subject(s) for their records.  The subject(s) 
may withdraw consent at any time throughout the course of the trial.  The rights and welfare of 
the subject(s) will be protected by emphasizing to them that the quality of their medical care will 
not be adversely affected if they decline to participate in this study. 
Study personnel may employ recruitment efforts prior to obtaining study consent if a patient-
specific screening consent is on record or if the IRB has agreed that chart review is allowed 
without a fully executed screening consent.  In cases where there is not a patient-specific 
screening consent on record, site clinical staff may pre-screen via chart review and refer potential 
subjects to the research staff.  Research staff would obtain written consent per the standard 
informed consent process before conducting protocol-specific screening activities. 
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. 
9.3 
Consent for Future Use of Stored Specimens and Data 
Residual samples/specimens are those that are left over after protocol-specified testing and this 
study has been completed.  Subjects may be asked for permission to keep any remaining 
(residual) 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 this permission 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 with investigators at the participating site and with other investigators at other 
institutions. The recipients of specimens will be informed that these specimens have a NIH 
certificate of confidentiality.  The information provided to the recipient will not contain direct 
identifiable information.  Use of the specimens will require review by an IRB. 
Non-protocol Extra Samples 
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 allows the 
option to choose that option. It is anticipated that up to 5 mL of serum from venous blood 
samples 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 use 
clinical samples will be stored indefinitely at a central clinical storage facility. 


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Residual specimens will be available upon the completion of this trial.  Extra samples/specimens 
collected during this study may be requested from DMID CMS while this study is ongoing or 
after the study, after IRB review. 
There are no benefits to subjects in the collection, storage and subsequent future use of their 
samples/specimens.  Future use samples/specimens will not be sold or used directly for 
production of any commercial product.  No genetic tests will be performed on 
samples/specimens.  Each sample/specimen will be encoded (labeled) only with a barcode and a 
unique tracking number that connects to a code key at the study site.  Restricted access to the 
code key is maintained by the PI to protect subject confidentiality.  Reports from future research 
studies performed using subjects’ samples/specimens will NOT be kept in their health records. 
Subjects may be given the option to decide if they want their residual specimens to be used for 
future research or have these specimens destroyed at the end of this trial, or this permission may 
be a condition of study participation.  If given the option, the subject’s decision can be changed 
at any time by notifying the study doctors or nurses in writing.  However, if the subject originally 
consents to the future use of residual specimens and subsequently changes his/her decision, any 
data from a previously collected specimen may be used for future research. 
9.4 
Exclusion of Women, Minorities, and Children (Special Populations) 
This trial will be inclusive of all subjects age 18 years and above who meet the Subject Inclusion 
Criteria (see Section 5.1.1) and do not meet the Subject Exclusion Criteria (see Section 5.1.2), 
regardless of religion, sex, or ethnic background. Should the outcome of this trial be deemed 
acceptable, additional trials may be initiated, including those in other populations. 
It is unknown if the 2017 H7N9 IIV with or without MF59® adjuvant poses any risks to an 
unborn child. The available data for women who become pregnant during clinical trials of 
MF59®-adjuvanted (pre) pandemic influenza vaccines do not suggest any causal relationship 
between adverse pregnancy outcomes and receipt of an MF59®-adjuvanted vaccine. Women of 
childbearing age who have undergone sterilization via tubal sterilization, bilateral oophorectomy, 
salpingectomy, hysterectomy, or successful Essure® placement (permanent, non-surgical, non-
hormonal sterilization) with documented radiological confirmation at least 90 days after the 
procedure are considered sterilized.  All other women of childbearing age who are still 
menstruating or < 1 year out from the last menses if menopausal must agree to practice highly 
effective contraception that may include, but not limited to, non-male sexual relationships, 
abstinence from sexual intercourse with a male partner, monogamous relationship with  
vasectomized partner who has been vasectomized for 180 days or more prior to the subject 
receiving the first study vaccination, male or female condoms with spermicide or with the use of 
applied spermicide, intrauterine devices, NuvaRing®, and licensed hormonal methods such as 
implants, injectables, or oral contraceptives (“the pill”),  with use of a highly effective method of 


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contraception for a minimum of 30 days prior to study product exposure and agree to practice 
highly effective contraception for the duration of study product exposure, including 60 days after 
their last study vaccination. A highly effective method of contraception is defined as one that 
results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. In 
addition to contraceptive use, all women of childbearing potential will be required to have a 
negative urine or serum pregnancy test within 24 hours prior to each study vaccination. If a 
female subject becomes pregnant while participating in this trial, we will ask her permission to 
follow-up with her about her health and the health of her baby through pregnancy outcome. 
Children will not be included in this trial as presently there are no safety or efficacy data in 
adults. 
9.5 
Subject Confidentiality 
Subject confidentiality is strictly held in trust by the participating investigators, their staff, and 
the sponsor(s) and their agents. This confidentiality includes documentation, investigation data, 
subject’s clinical information, and all other information generated during participation in the 
study.    
No information concerning the study or the data generated from the study will be released to any 
unauthorized third party without prior written approval of the DMID and the subject.  Subject 
confidentiality will be maintained when study results are published or discussed in conferences. 
The study monitor or other authorized representatives of the sponsor or governmental regulatory 
agencies may inspect all documents and records required to be maintained by the investigator, 
including but not limited to, medical records (office, clinic, or hospital) and pharmacy records 
for the subjects in this study. The clinical study site will permit access to such records.  All 
records will be kept locked and all computer entry and networking programs will be carried out 
with coded numbers only and with password protected systems.  All non-clinical specimens, 
evaluation forms, reports, and other records that leave the site will be identified only by a coded 
number.   
9.6 
Certificate of Confidentiality 
To protect privacy we have 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, for example, if there is a court subpoena. 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 


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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.   
9.7 
Costs, Subject Compensation, and Research Related Injuries 
There is no cost to subjects for the research tests, procedures, and study product while taking part 
in this trial. Procedures and treatment for clinical care may be billed to the subject, subject’s 
insurance or third party.  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 site PI that an injury occurred to a subject as a direct result of the tests 
or treatments that are done for this trial, then referrals to appropriate health care facilities will be 
provided to the subject. Study personnel will try to reduce, control, and treat any complications 
from this trial. Immediate medical treatment may be provided by the participating site.   No 
financial compensation will be provided to the subject by the NIAID, NIH to the subject, or by 
the participating 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 Seqirus and adjuvant (MF59®) manufactured by Seqirus), are covered under the 
Public Readiness and Emergency Preparedness Act (PREP Act), as described in Section 2.1.1. 
 


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10 
STATISTICAL CONSIDERATIONS 
10.1 
Study Hypotheses 
This Phase II study is not designed to test a formal null hypothesis. Rather, it is intended to 
obtain sufficient data to obtain meaningful estimates of the immune response induced by this 
vaccine and to uncover any safety issues that occur at a sufficiently high rate that they might be 
observed in a study of this size. The sample size facilitates formal testing of selected hypotheses 
as discussed in Section 10.2, along with the probability of observing safety outcomes and the 
precision of immunogenicity outcomes. 
10.2 
Sample Size Considerations 
This study is planned to enroll 106 subjects in each adjuvanted treatment arm, and 53 subjects in 
the unadjuvanted treatment arm. Randomization at each site will be stratified by prior receipt of 
seasonal influenza vaccines, however there is no enrollment target for these strata.  The sample 
size for this study was selected to obtain preliminary estimates in a time critical manner. While 
this study is not designed to test any specific null hypothesis, the following tables illustrate the 
precision and power that is available for select estimates and comparisons of interest. 
Table 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 arm (N = 53, 106), and for all subjects receiving adjuvanted vaccine 
(N = 318). 
Table 8: Power (%) to Detect Safety Events: 
Event 
Frequency 
N = 53 
N = 106 
N = 318 
≥10% 
Very Common 
>99 
>99 
>99 
≥1% 
Common 
41 
65 
95 
≥0.1% 
Uncommon 
45 
10 
27 
≥0.01% 
Rare 
<1 
1 
3 
Binomial confidence intervals (CI) are widest (have the least precision) when the response rate is 
50%.  
 
 
 is presented to indicate the worst case scenario for precision of observed exact (Clopper-
Pearson) binomial confidence intervals. 


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Table 9: Precision of Binomial Confidence Intervals: 
N 
95% CI 
53 
36-64 
106 
40-60 
318 
44-56 
 
Table 10 illustrates the minimum detectable differences in the proportion of subjects responding 
(e.g., attaining seroconversion or a titer ≥40) between two adjuvanted treatment arms using a 
two-sided Likelihood Ratio Test and alpha = 0.05. 
Power calculations will assume n=100 per adjuvanted group and n=50 for the unadjuvanted 
group. Based on previous DMID A/H7N9 trials it is expected 5% of enrolled subjects may be 
excluded from analysis of the primary endpoint.  
Table 10: Minimum Detectable Difference in Proportion Responders with 80% Power 
Assumed Proportion of subjects with titer ≥40 in 
comparator arm 
Minimum Detectable 
Difference 
(N = 100) 
0.40 
0.20 
0.50 
0.20 
0.60 
0.19 
0.70 
0.17 
0.80 
0.14 
0.90 
0.09 
Per FDA guidance [67], the lower confidence limit on the appropriate point estimate excluding 
equality (i.e., a difference [adjuvanted – unadjuvanted] greater than zero in HAI antibody 
response rates) may be sufficient to demonstrate the added value of the adjuvant. Table 11 shows 
the lower bound of the 95% confidence interval for the differenc42 in the proportion responders 
between the adjuvanted and unadjuvanted arms (e.g. 15 mcg + MF59® minus 15 mcg 
unadjuvanted) assuming the proportion of responders in the unadjuvanted arm is 0.10 and 
considering a range for the proportion of responders in the adjuvanted arm ranges from 0.50 to 
0.90.  
Table 11: Lower Confidence bound2 for difference in proportion of responders between 
adjuvanted (N = 100) and unadjuvanted (N = 50) arms, 18-64 years stratum 
Adjuvanted Arm 
Unadjuvanted 
Arm 
Difference 
Lower Confidence 
Bound 
0.50 
0.10 
0.40 
0.26 


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0.60 
0.10 
0.50 
0.36 
0.70 
0.10 
0.60 
0.46 
0.80 
0.10 
0.70 
0.56 
0.90 
0.10 
0.80 
0.67 
10.3 
Treatment Assignment Procedures 
10.3.1 
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 
Data Coordinating Center’s (SDCC) AdvantageEDCSM (Electronic Data Capture System). 
Once consented and upon entry of demographic data and confirmation of eligibility for this trial, 
the subject will be enrolled, randomly assigned to 1 of 4 treatment groups. All subjects will 
receive 2 vaccinations; the same dose will be given to the subject at both the first and second 
vaccination. Subjects will be randomized with allocation 2:2:2:1 into 4 groups, stratified by site 
(see Table 1) and by prior receipt of at least one of the 2017-2018 and/or 2018-2019 seasonal 
influenza vaccines to receive IM 2017 H7N9 IIV at 3.75 mcg, 7.5 mcg or 15 mcg at Days 1 and 
22 with MF59® adjuvant or 15 mcg at Days 1 and 22 administered without adjuvant. 
Enrollment of subjects will be done online using the enrollment module of AdvantageEDCSM. 
The randomization code will be prepared by statisticians at the SDCC and included in the 
enrollment module for this trial. AdvantageEDCSM will assign each subject to a treatment arm 
after the demographic and eligibility data have been entered into the system. A designated 
individual at each participating VTEU site will be provided with a code list for emergency 
unblinding purposes, which will be kept in a secure place. 
Instructions for use of the enrollment module are included in the AdvantageEDCSM User’s 
Guide. Manual back-up procedures and instructions are provided for use in the event that a 
participating VTEU site temporarily loses access to the Internet or the online enrollment system 
is unavailable. 
10.3.2 
Masking Procedures 
This is a double-blind clinical trial. 
Subjects, investigators, study personnel performing any study-related assessments following 
study vaccine administration are blinded to study treatment. Laboratory personnel performing 
HAI and Neut antibody assays will receive serum samples blinded to subject ID number and 
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The randomization scheme will be generated by the DCC and provided to unblinded study 
personnel (i.e., research pharmacists performing study vaccine preparations and unblinded study 
vaccine administrators) at the participating VTEU sites. 
The unblinded study vaccine administrator is a study personnel member credentialed to 
administer vaccines and may also participate in dose preparation, but will not be involved in 
study-related assessments or have subject contact for data collection following study vaccine 
administration. 
The Data and Safety Monitoring Board (DSMB) may receive data in aggregate and presented by 
treatment arm. The DSMB may also be provided with expected and observed rates of the 
expected AEs in an unblinded fashion, and may request the treatment arm be unblinded for an 
individual subject if required for safety assessment. The DSMB will review grouped and 
unblinded data in the closed session only. 
10.4 
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 8.7.2. 
A set of “topline” immunogenicity and safety tables produced on an expedited timeline will be 
prepared as described in section 10.6; though this report will be released while subjects remain in 
the trial for long-term safety follow-up, it will be considered the final analysis of these data. 
Emergent public health needs may dictate additional interim safety, reactogenicity, and/or 
immunogenicity analyses be performed on available information at any time during the trial. If 
this occurs, immunogenicity data will be analyzed as results are available from the central 
immunogenicity laboratory. 
10.4.1 
Interim Safety Review 
An interim safety review may include enrollment and demographic information, medical history, 
concomitant medications, physical assessments, dosing compliance, and solicited and unsolicited 
AE/SAEs. Additional data may be requested by the DSMB, and interim statistical reports may be 
generated as deemed necessary and appropriate by DMID. The DSMB may receive data in 
aggregate and presented by treatment arm. The DSMB may also be provided with expected and 
observed rates of the expected AEs in an unblinded fashion, and may request the treatment 
assignment be unblinded for an individual subject if required for safety assessment. The DSMB 


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will review grouped and unblinded data in the closed session only. The DSMB will meet and 
review this data at scheduled time points or ad hoc as needed during this trial as defined in the 
DSMB charter. As an outcome of each review/meeting, the DSMB will make a recommendation 
as to the advisability of proceeding with study vaccinations (as applicable), and to continue, 
modify, or terminate this trial. 
Additionally, this trial will be monitored to determine if any of the halting rules described in 
Section 8.6.1 are met. 
10.4.2 
Interim Immunogenicity or Efficacy Review 
Should emergent public health needs dictate interim immunogenicity review, immune responses 
will be summarized in terms of strain-specific 2017 A/H7N9 HAI and Neut antibody titers. Any 
immunogenicity reports would be provided by the SDCC to the DMID Scientific Lead and CPM, 
and the DSMB. Reports would include data summarized by treatment arm.  
10.5 
Final Analysis Plan 
Clinical, safety, and reactogenicity data through approximately 180 days after the second study 
vaccination will represent the primary clinical database for this trial. Once the last subject 
completes the visit that occurs approximately 180 days after second study vaccination and all 
HAI and Neut results are received, a  “topline” subset of the immunogenicity and safety tables 
will be provided to DMID on an expedited timeline.  These analyses may be made available to 
the sponsor for planning subsequent trials and to the lead PI for publication. These analyses will 
not be used to make any decisions concerning the conduct of this trial. As it is anticipated that 
subjects will remain in long term safety follow-up at the time of these analyses, blinded 
investigators and DMID medical monitors not involved in the analysis, publication, or clinical 
study report preparation will be responsible for assessing SAEs and MAAEs including PIMMCs 
and new onset chronic medical conditions until all subjects have completed the final follow-up 
visit. All analyses of data included in the topline tables for early release will be considered the 
final analysis of these data, and also included in the final clinical study report (CSR). 
Analysis of exploratory immunogenicity endpoints may be performed and released as the data 
are available from the research laboratory. Any such analyses would be considered the final 
analysis for the endpoint, and included in the CSR. The final CSR will be completed after the 
last subject’s last visit is completed, and the final clinical database including all long term safety 
follow-up data is cleaned, monitored and locked. Additional exploratory immunogenicity 
endpoint data not available at the time of CSR preparation may be included in an addendum to 
the CSR. 
A formal statistical analysis plan will be developed and finalized prior to unblinding for any 


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analysis, which defines the analyses to be included in the topline tables and the final CSR. 
10.5.1 
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 
were reported. For analyses using the mITT population, subjects will be grouped based on 
randomized treatment arm.  
The per protocol (PP) population includes all subjects in the mITT subset with the following 
exclusions: 
• Data from all available visits for subjects found to be ineligible at baseline. 
• Data from all visits subsequent to major protocol deviations, such as: 
• Second study vaccination not received, 
• Second study vaccination received out of window, 
• Receipt of non-study licensed live vaccine within 30 days before or after each study 
vaccination, 
• Receipt of non-study licensed inactivated vaccine within 14 days before or after each study 
vaccination, 
• Receipt of immunosuppressive therapy (e.g., corticosteroids) within 30 days before or after 
each study vaccination. 
• Data from any visit that occurs substantially out of window. 
For analyses using the PP population, subjects will be grouped based on study vaccinations 
received. 
10.5.2 
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-
7 post each study vaccination) and as the maximum severity over all 8 days. Additionally, 
solicited AEs will be analyzed by taking the most severe response over the follow-up period, 


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dichotomizing into a binary variable (none versus mild, moderate, or severe) and using standard 
techniques, such as exact confidence intervals, to summarize the proportion of subjects reporting 
each symptom, any injection site symptom, and any systemic symptom. Summaries of solicited 
AEs will be presented separately for each study vaccination as well as overall study vaccinations 
by treatment arm. The proportion of subjects reporting symptoms may be compared between 
treatment arms using Chi-square or Fisher’s exact test. The proportion of subjects reporting 
solicited symptoms between the different study vaccinations (i.e., first and second) will be 
compared using McNemar’s test. 
Unsolicited AEs will be coded by Medical Dictionary for Regulatory Activities (MedDRA) for 
preferred term and system organ class (SOC). The numbers of SAEs, MAAEs, including 
NOCMCs, and PIMMCs are likely to be small in this trial and will be reported by detailed 
listings showing the event description, MedDRA preferred term and SOC, relevant dates (study 
vaccinations and AEs), severity, relatedness, and outcome for each event. Non-serious 
unsolicited AEs will be summarized as number and percentage of subjects reporting at least one 
event in each MedDRA preferred term and SOC, cross tabulated by severity and relationship to 
study product. Additionally, the proportion of subjects and exact 95% confidence intervals of 
AEs in aggregate and by MedDRA categories will be computed. 
10.5.3 
Immunogenicity Data  
Summaries and analysis of immunogenicity data will be presented for the mITT and PP 
populations. 
Immune responses in terms of strain-specific 2017 H7N9 HAI and Neut antibody titers will be 
summarized by treatment arm at each time point. Analyses will include percentage of subjects 
with a titer ≥40, percentage of subjects achieving seroconversion (defined as either a pre-
vaccination titer <10 and a post-vaccination titer ≥40 or a pre-vaccination titer ≥10 and a 
minimum four-fold rise in post-vaccination antibody titer), and GMTs along with corresponding 
95% confidence intervals. Descriptive summary statistics will be provided for all assays and time 
points. The correlation between HAI and Neut antibody titers will be evaluated. Plots such as 
reverse cumulative distributions or longitudinal presentations of GMTs will be presented. 
Additionally, the immune response, as described above, will be summarized by available 
covariates, such as age, sex, body mass index, and prior receipt of seasonal influenza vaccine(s), 
and these covariates may be considered statistical modeling. As an exploratory analysis, models 
will be developed to evaluate the relationship between dosage and adjuvant on immune response. 
For example, logistic regression may be used to examine the relationship of proportion of 
responders with dosage and adjuvant, and available covariates may be considered for inclusion in 
the model. 
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may be assessed at baseline, and 8, 22, 29, 43 and 202 after receipt of the first study vaccination.  
For each time point summaries will include percentage of subjects with detectable N9 NA 
response (to be defined in SAP following assay development and selection) and GMTs along 
with corresponding 95% confidence intervals. Descriptive summary statistics will be provided 
for all assays and time points. The correlation of N9 NA response with HAI and Neut antibody 
titers will be evaluated, and plots such as reverse cumulative distributions or longitudinal 
presentations of GMTs will be presented. 
Further, a determination of the NA content of the 2017 H7N9 IIV is planned if an assay becomes 
available and may be used to correlate the N9 NA elicited antibody responses to the NA content 
of the 2017 H7N9 IIV. Detectable NA antibody responses and GMTs will be summarized and 
evaluated for a dose response.  If the NA content is available, NA antibody responses will be 
stratified by NA content, and statistical modeling may be used to examine the relationship of NA 
response with NA vaccine content, HA antigen dosage, and adjuvant.  
At least a subset of samples will also be tested for cross-reactive serum HAI and Neut antibody 
responses to antigenically drifted variants of influenza A/H7 viruses. Strain-specific results will 
be summarized using descriptive statistics as described above, correlations with 2017 H7N9 
responses, and association with study vaccine dose and adjuvant. 
Further immunogenicity testing and/or analyses may be carried out in the future based upon 
subjects’ prior receipt of non-seasonal influenza vaccines, including type (inactivated or live 
attenuated), what subtype (e.g. A/H3, A/H5, A/H9) and approximate date of vaccination. 
10.5.4 
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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11 
SOURCE DOCUMENTS ACCESS TO SOURCE 
DATA/DOCUMENTS 
Each participating site will maintain appropriate medical and research records in compliance 
with ICH E6, section 4.9, and regulatory and institutional requirements for the protection of 
confidentiality of subjects. Each 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, evaluation of 
the study safety and progress. These representatives will be permitted access to all source data 
and source documents, which include, but are not limited to, hospital records, clinical and office 
charts, laboratory notes, memoranda, subjects’ Memory Aid or 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 clinical trial.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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12 
QUALITY CONTROL AND QUALITY ASSURANCE 
Following a written DMID-accepted site quality management plan, each participating site(s) and 
its subcontractors are responsible for conducting routine quality assurance (QA) and quality 
control (QC) activities to internally monitor study progress and protocol compliance. The site PI 
will provide direct access to all study-related sites, source data/data collection forms, and reports 
for the purpose of monitoring and auditing by the sponsor, and inspection by local and regulatory 
authorities. The site PI will ensure all study personnel are appropriately trained and training 
documentation is current and maintained on site. 
The DCC 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 site(s) for clarification and resolution. 


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13 
DATA HANDLING AND RECORD KEEPING 
13.1 
Data Management Responsibilities 
The investigator is responsible to ensure the accuracy, completeness, legibility, and timeliness of 
the data reported. All source data collection forms should be completed in a neat, legible manner 
to ensure accurate interpretation of data. Black or blue permanent 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. 
Copies of the electronic CRF (eCRF) will be provided for use as source data collection forms 
and maintained for recording data for each subject enrolled in the study.  Data reported in the 
eCRF derived from the source data collection forms should be consistent or the discrepancies 
should be explained. 
The sponsor and/or its designee will provide guidance to the site PI and other study personnel on 
making corrections to the data collection forms and eCRF. 
13.2 
Data Coordinating Center/Biostatistician Responsibilities 
Data collection is the responsibility of the study personnel at each participating clinical site under 
the supervision of the site PI. During this trial, the site PI must maintain complete and accurate 
documentation for the study. 
The Data Coordinating Center for this study will be responsible for data management, quality 
review, analysis, and reporting of the study data. 
13.3 
Data Capture Methods 
Clinical (including, but not limited to, AE/SAEs, concomitant medications, medical history, 
physical assessments), and reactogenicity will be collected on data collection forms by study 
personnel then entered into eCRF via a 21 CFR 11-compliant Internet Data Entry System 
provided by the study data coordinating center. The data system includes password protection 
and internal quality checks, such as automatic range checks, to identify data that appear 
inconsistent, incomplete, or inaccurate. 
13.4 
Types of Data 
Data for this trial will include clinical, safety, and outcome measures (e.g., reactogenicity and 
immunogenicity data). 


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13.5 
Study Records Retention 
Study records and reports including, but not limited to, CRFs, source documents, ICFs, 
laboratory test results, and study drug disposition records will be retained for a minimum of 2 
years after a marketing application is approved for the study product for which it is being 
investigated; or, if no application is to be filed or if the application is not approved for the study 
product, until 2 years after the investigation is discontinued and the FDA has been notified.  
These documents will be retained for a longer period, however, if required by local regulations. 
ICFs for future use will be maintained as long as the sample/specimen exists.  
No records will be destroyed without written consent of the sponsor.  It is the responsibility of 
the sponsor to inform the investigator when these documents no longer need to be retained. The 
participating VTEU site(s) must contact DMID for authorization prior to the destruction of any 
study records. 


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14 
CLINICAL MONITORING 
Site monitoring is conducted to ensure that the human subjects’ protections, study and laboratory 
procedures, study intervention administration, and data collection processes are of high quality 
and meet sponsor, ICH/GCP guidelines and applicable regulations, and that this trial is 
conducted in accordance with the protocol, protocol-specific MOP and applicable sponsor 
standard operating procedures. DMID, the sponsoring agency, or its designee will conduct site-
monitoring visits as detailed in the clinical monitoring plan. 
Site visits will be made at standard intervals as defined by DMID and may be made more 
frequently as directed by DMID. Monitoring visits will include, but are not limited to, review of 
regulatory files, accountability records, eCRFs, ICFs, medical and laboratory reports, and 
protocol and GCP compliance. Site monitors will have access to each participating site, study 
personnel, and all study documentation according to the DMID-approved site monitoring plan. 
Study monitors will meet with site PIs to discuss any problems and actions to be taken and 
document visit findings and discussions. 
 
 


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PUBLICATION POLICY 
Following completion of the study, the lead PI is expected to publish the results of this research 
in a scientific journal.  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 plans not 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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LITERATURE REFERENCES 
1. 
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2. 
Fouchier, R.A., et al., Avian influenza A virus (H7N7) associated with human 
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3. 
Lindstrom, S., et al., Human infections with novel reassortant influenza A(H3N2)v 
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Peiris, M., et al., Human infection with influenza H9N2. Lancet, 1999. 354(9182): p.  
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5. 
Perez-Padilla, R., et al., Pneumonia and respiratory failure from swine-origin influenza A 
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Subbarao, K., et al., Characterization of an avian influenza A (H5N1) virus isolated from 
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Oxford, J.S., Influenza A pandemics of the 20th century with special reference to 1918: 
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Patriarca, P.A. and N.J. Cox, Influenza pandemic preparedness plan for the United 
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Galasso, G.J., F.J. Tyeryar, Jr., and J.R. La Montagne, Overview of clinical trials of 
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La Montagne, J.R., et al., Summary of clinical trials of inactivated influenza vaccine - 
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11. 
Couch, R.B. and J.A. Kasel, Immunity to influenza in man. Annu Rev Microbiol, 1983. 
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12. 
Couch, R.B., et al., Antibody correlates and predictors of immunity to naturally 
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Memoli, M.J., et al., Evaluation of Antihemagglutinin and Antineuraminidase Antibodies 
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14. 
Ennis, F.A., et al., Correlation of laboratory studies with clinical responses to A/New 
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Gross, P.A., et al., Immunization of elderly people with high doses of influenza vaccine. J 
Am Geriatr Soc, 1988. 36(3): p. 209-12. 
16. 
Keitel, W.A., et al., High doses of purified influenza A virus hemagglutinin significantly 
augment serum and nasal secretion antibody responses in healthy young adults. J Clin 
Microbiol, 1994. 32(10): p. 2468-73. 


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17. 
Matzkin, H. and E. Nili, Accidental tenfold overdose of influenza vaccine: a clinical and 
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18. 
Mostow, S.R., et al., Inactivated vaccines. 1. Volunteer studies with very high doses of 
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19. 
Palache, A.M., et al., Antibody response after influenza immunization with various 
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20. 
Remarque, E.J., et al., Improvement of the immunoglobulin subclass response to 
influenza vaccine in elderly nursing-home residents by the use of high-dose vaccines. Vaccine, 
1993. 11(6): p. 649-54. 
21. 
Ruben, F.L. and G.G. Jackson, A new subunit influenza vaccine: acceptability compared 
with standard vaccines and effect of dose on antigenicity. J Infect Dis, 1972. 125(6): p. 656-64. 
22. 
Ruben, F.L., C.W. Potter, and C.H. Stuart-Harris, Humoral and secretory antibody 
responses to immunization with low and high dosage split influenza virus vaccine. Arch Virol, 
1975. 47(2): p. 157-66. 
23. 
Keitel, W.A., et al., Increasing doses of purified influenza virus hemagglutinin and 
subvirion vaccines enhance antibody responses in the elderly. Clin Diagn Lab Immunol, 1996. 
3(5): p. 507-10. 
24. 
Couch, R.B., et al., A randomized clinical trial of an inactivated avian influenza A 
(H7N7) vaccine. PLoS One, 2012. 7(12): p. e49704. 
25. 
Treanor, J.J., et al., Safety and immunogenicity of an inactivated subvirion influenza A 
(H5N1) vaccine. N Engl J Med, 2006. 354(13): p. 1343-51. 
26. 
Atmar, R.L. and W.A. Keitel, Adjuvants for pandemic influenza vaccines. Curr Top 
Microbiol Immunol, 2009. 333: p. 323-44. 
27. 
Bresson, J.L., et al., Safety and immunogenicity of an inactivated split-virion influenza 
A/Vietnam/1194/2004 (H5N1) vaccine: phase I randomised trial. Lancet, 2006. 367(9523): p. 
1657-64. 
28. 
Keitel, W.A., et al., Safety and immunogenicity of an inactivated influenza A/H5N1 
vaccine given with or without aluminum hydroxide to healthy adults: results of a phase I-II 
randomized clinical trial. J Infect Dis, 2008. 198(9): p. 1309-16. 
29. 
Carmona, A., et al., Immunogenicity and safety of AS03-adjuvanted 2009 influenza A 
H1N1 vaccine in children 6-35 months. Vaccine, 2010. 28(36): p. 5837-44. 
30. 
Diez-Domingo, J., et al., Immunogenicity and Safety of H5N1 A/Vietnam/1194/2004 
(Clade 1) AS03-adjuvanted prepandemic candidate influenza vaccines in children aged 3 to 9 
years: a phase ii, randomized, open, controlled study. Pediatr Infect Dis J, 2010. 29(6): p.  
e35-46. 
31. 
McElhaney, J.E., et al., AS03-adjuvanted versus non-adjuvanted inactivated trivalent 
influenza vaccine against seasonal influenza in elderly people: a phase 3 randomised trial. 
Lancet Infect Dis, 2013. 13(6): p. 485-96. 


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32. 
Vogel, F.R., et al., Emulsion-based adjuvants for influenza vaccines. Expert Rev 
Vaccines, 2009. 8(4): p. 483-92. 
33. 
Cruz-Valdez, A., et al., MF59-adjuvanted influenza vaccine (FLUAD(R)) elicits higher 
immune responses than a non-adjuvanted influenza vaccine (Fluzone(R)): a randomized, 
multicenter, Phase III pediatric trial in Mexico. Hum Vaccin Immunother, 2017: p. 0. 
34. 
Nicholson, K.G., et al., Safety and antigenicity of non-adjuvanted and MF59-adjuvanted 
influenza A/Duck/Singapore/97 (H5N3) vaccine: a randomised trial of two potential vaccines 
against H5N1 influenza. Lancet, 2001. 357(9272): p. 1937-43. 
35. 
El Sahly, H., et al., A Phase II Randomized, Partially-Blinded, Controlled, Trial in 
Healthy Adults Aged 65 Years and Older to Assess the Safety, Reactogenicity, and 
Immunogenicity of an MF59-Adjuvanted, Monovalent Inactivated Influenza A/H7N9 Virus 
Vaccine Administered Intramuscularly at Different Intervals and Dosages. Manuscript in 
preparation. 
36. 
Chen, W.H., et al., Safety, Reactogenicity, and Immunogenicity of Inactivated 
Monovalent Influenza A(H5N1) Virus Vaccine Administered With or Without AS03 Adjuvant. 
Open Forum Infect Dis, 2014. 1(3): p. ofu091. 
37. 
Jackson, L.A., et al., Effect of Varying Doses of a Monovalent H7N9 Influenza Vaccine 
With and Without AS03 and MF59 Adjuvants on Immune Response: A Randomized Clinical 
Trial. JAMA, 2015. 314(3): p. 237-46. 
38. 
Jackson, L.A., et al., Immunogenicity and safety of varying dosages of a monovalent 2009 
H1N1 influenza vaccine given with and without AS03 adjuvant system in healthy adults and 
older persons. J Infect Dis, 2012. 206(6): p. 811-20. 
39. 
Mulligan, M.J., et al., Point-of-Use Mixing of Influenza H5N1 Vaccine and MF59 
Adjuvant for Pandemic Vaccination Preparedness: Antibody Responses and Safety. A Phase 1 
Clinical Trial. Open Forum Infect Dis, 2014. 1(3): p. ofu102. 
40. 
Mulligan, M.J., et al., Serological responses to an avian influenza A/H7N9 vaccine mixed 
at the point-of-use with MF59 adjuvant: a randomized clinical trial. JAMA, 2014. 312(14): p. 
1409-19. 
41. 
Atmar, R.L., et al., Safety and immunogenicity of nonadjuvanted and MF59-adjuvanted 
influenza A/H9N2 vaccine preparations.  Clin Infect Dis, 2006. 43(9): p. 1135-42. 
42. 
Wu, H., et al., Novel reassortant influenza A(H5N8) viruses in domestic ducks, eastern 
China. Emerg Infect Dis, 2014. 20(8): p. 1315-8. 
43. 
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. 
44. 
Analysis of recent scientific information on avian influenza A(H7N9) virus. WHO  
Influenza Update, 2017. 
45. 
Influenza at the human-animal interface.  Summary and Assessment, 26 January to 2 
March 2018.  WHO Monthly Influenza Risk Assessment Summary, 2 March, 2018. 
46. 
WHO Emergencies preparedness, response- Disease Outbreak News 5 April 2017. 


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47. 
Zhou, J., et al., Biological features of novel avian influenza A (H7N9) virus. Nature, 
2013. 499(7459): p. 500-3. 
48. 
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. 
49. 
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. 
50. 
Kilbourne, E.D., et al., Purified influenza A virus N2 neuraminidase vaccine is 
immunogenic and non-toxic in humans.  Vaccine, 1995. 13(18): p. 1799-803. 
51. 
Bart, S.A. et al., A cell culture-derived MF59-adjuvanted A/H7N9 vacine is immunogenic 
in adults.  Sci Transl Med, 2014.  6(234): p. 1-10. 
52. 
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. 
53. 
Grohskopf L.A., et al., Prevention and control of seasonal influenza vaccines. MMWR 
Recomm Rep, 2016. 65(5): p. 1-54. 
54. 
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. 
55. 
Haber, P., et al., Guillain-Barre syndrome following influenza vaccination. JAMA, 2004. 
292(20): p. 2478-81. 
56. 
De Wals, P., et al., Risk of Guillain-Barre syndrome following H1N1 influenza 
vaccination in Quebec. JAMA, 2012. 308(2): p. 175-81. 
57. 
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. 
58. 
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. 
59. 
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. 
60. 
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. 
61. 
Dodd, C.N., et al., International collaboration to assess the risk of Guillain Barre 
Syndrome following Influenza A (H1N1) 2009 monovalent vaccines. Vaccine, 2013. 31(40): p. 
4448-58. 
62. 
Tsai, T.F. FLUAD®-MF59-adjuvanted influenza vaccine in older adults.  Infect 
Chemother, 2013, 45(2): p. 159-174. 
63. 
Black, S. et al., Safety of MF59-adjuvanted versus non-adjuvanted influenza vaccine in 
children and adolescents: an integrated analysis. Vaccine, 2010. 28(45): p. 7331-6. 


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64. 
Pelligrini, M. et al., MF-59-adjuvanted versus non-adjuvanted influenza vaccine:  an 
integrated analysis from a large safety database.  Vaccine, 2009. 27(49): p. 6959-65. 
65. 
Tsai, T., et al., Exposure to MF59-adjuvanted influenza vaccines during pregnancy--a 
retrospective analysis. Vaccine, 2010. 28(7): p. 1877-80. 
66. 
Heikkinen T., et al., Safety of MF59-adjuvanted A/H1N1 influenza vaccine in pregnancy: 
a comparative cohort study.  Am J Obstet Gynecol, 2012. 207: p. e1-8. 
67. 
FDA, Guidance for Industry: Clinical Data Needed to Support the Licensure of Seasonal 
Inactivated Influenza Vaccines, 2007. 
 
 
 
 
 
 


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APPENDICES 
APPENDIX A: SCHEDULE OF PROCEDURES AND EVALUATIONS 
 
APPENDIX B. LIST OF POTENTIALLY IMMUNE MEDIATED MEDICAL CONDITIONS


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APPENDIX A: SCHEDULE OF PROCEDURES AND EVALUATIONS 
Study Visit 
V00 
V01 
V02 
V03 
V04 
V05 
V06 
V07 
V08 
V09 
V10 
V11 
Early Term 
Unscheduled 
Study Day Post 1st 
Vaccination 
Screen 
Optional  
D-28 to  
-1 
Dose 1 
D1 
D4 
±1d 
D8 
+2d 
D22 
+7d 
D25 
D29 
D43 
D82 
D142 
D202 
D387 
 
 
Study Day Post 2nd 
Vaccination 
 
 
 
 
Dose 2 
D1 
D4 
±1d 
D8 
+2d 
D22 
+7d 
D61 
±7d 
D121 
±14d 
D181
±14d 
D366 
±14d 
 
 
Obtain Informed 
Consent 
X∞ 
X∞¬ 
 
 
 
 
 
 
 
 
 
 
 
 
Collect Demographic 
Information 
X 
X†* 
 
 
 
 
 
 
 
 
 
 
 
 
Review Eligibility 
Criteria 
X 
X†¬ 
 
 
X† 
 
 
 
 
 
 
 
 
 
Medical History@ 
X 
X†¬ 
X 
X 
X† 
X 
X 
X 
 
 
X 
 
X 
X(if indicated) 
Concomitant 
Medications5 
X 
X†¬ 
X 
X 
X† 
X 
X 
X 
X 
X 
X 
 
X (if within 180 
days after last 
study 
vaccination) 
X (if prior to 180 
days after last study 
vaccination) 
Vital Signs$ (Oral 
Temperature%, Pulse, 
and BP) 
X 
X† 
 
 
X†2 
 
 
 
 
 
 
 
X (may be 
obtained if 
indicated) 
X (may be obtained 
if indicated) 
Height and Weight 
X 
X†* 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination3 
X 
X†*6 
 
{X} 
{X}† 
 
{X} 
{X} 
 
 
{X} 
 
{X} 
{X} 
 
 
 
 
 
 


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Study Visit 
V00 
V01 
V02 
V03 
V04 
V05 
V06 
V07 
V08 
V09 
V10 
V11 
Early Term 
Unscheduled 
Study Day Post 1st 
Vaccination 
Screen 
Optional  
D-28 to  
-1 
Dose 1 
D1 
D4 
±1d 
D8 
+2d 
D22 
+7d 
D25 
D29 
D43 
D82 
D142 
D202 
D387 
 
 
Study Day Post 2nd 
Vaccination 
 
 
 
 
Dose 2 
D1 
D4 
±1d 
D8 
+2d 
D22 
+7d 
D61 
±7d 
D121 
±14d 
D181
±14d 
D366 
±14d 
 
 
Serum or Urine 
Pregnancy Test 
X^ 
X†^ 
 
 
X†^ 
 
 
 
 
 
 
 
 
 
Venous Blood 
Collection for Clinical 
Safety Laboratory 
Evaluations 
 
X1 
 
X1 
X1 
 
X1 
 
 
 
 
 
X (if within 7 
days after the 
last study 
vaccination) 
X (if indicated) 
Venous Blood 
Collection for 
Immunongenicity 
Assays 
 
X† 
 
X 
X†Ψ 
 
X 
X 
 
 
XΨ 
 
X (if within 21 
days after last 
study 
vaccination) 
X (if prior to 21 days 
after last study 
vaccination) 
Serum Sample 
Collected for Future 
Research4 
 
X† 
 
X 
X† 
 
X 
X 
 
 
 
X 
 
X(if within 21 
days after last 
study 
vaccination 
X(if prior to 21 days 
after last study 
vaccination 
Enrollment in 
AdvantageEDCSM and 
Randomization 
 
 
X† 
 
 
 
 
 
 
 
 
 
 
 
 
Pre-Administration 
Reactogenicity 
Assessments 
 
X† 
 
 
X† 
 
 
 
 
 
 
 
 
 
Study Vaccination 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
20-minute Evaluation 
After Study Vaccination 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
Examine Study 
Vaccination Site 
 
X 
 
X 
X 
 
X 
 
 
 
 
 
X (if within 7 
days after last 
study 
vaccination) 
X (if within 7 days 
after last study 
vaccination) 
 
 


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Study Visit 
V00 
V01 
V02 
V03 
V04 
V05 
V06 
V07 
V08 
V09 
V10 
V11 
Early Term 
Unscheduled 
Study Day Post 1st 
Vaccination 
Screen 
Optional  
D-28 to  
-1 
Dose 1 
D1 
D4 
±1d 
D8 
+2d 
D22 
+7d 
D25 
D29 
D43 
D82 
D142 
D202 
D387 
 
 
Study Day Post 2nd 
Vaccination 
 
 
 
 
Dose 2 
D1 
D4 
±1d 
D8 
+2d 
D22 
+7d 
D61 
±7d 
D121 
±14d 
D181
±14d 
D366 
±14d 
 
 
Post-Administration 
Reactogenicity 
Assessments 
 
X 
 
 
X 
 
 
 
 
 
 
 
X (if within 7 
days after last 
study 
vaccination) 
X (if within 7 days 
after last study 
vaccination) 
Distribute Memory Aid 
and Study-Related 
Materials 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
Review Memory Aid 
 
 
X 
X 
 
X 
X 
 
 
 
 
 
X (if within 7 
days after last 
study 
vaccination) 
X (if within 7 days 
after last study 
vaccination) 
AE Assessment 
 
X& 
X& 
X& 
X& 
X& 
X& 
X 
 
 
 
 
 
 
X 
SAEs/MAAEs/ 
NOCMCs/PIMMCs 
Assessment 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Phone Call 
 
 
X 
 
 
X 
 
 
X 
X 
 
X 
 
 
∞ Prior to performing any study procedures. 
† Prior to study vaccination.  
   Review results of safety laboratory evaluations¬ Review/confirm information or activity in subjects previously consented and screened 
@ Complete medical history will be obtained by interview of subjects at the first visit (either screening [optional] or on Day 1 prior to the first study vaccination) 
and interim medical history will be obtained by interview of subjects at subsequent visits. 
*    Not required if done at the optional screening visit 
$ Vital signs assessed on Day 1 prior to the first study vaccination will be considered as baseline. 
% Subjects must not eat or drink anything hot or cold, or smoke within 10 minutes prior to taking oral temperature. 
2 Vital signs are not required for subjects who are discontinued from receipt of the second study vaccination and are being followed for safety. 
3 At the screening (or baseline if not done at screening) visit, a physical examination will be performed on all subjects to include the following organs and organ 
systems: skin, head and neck, lungs, heart, liver, spleen, extremities, lymph nodes, abdomen, general appearance, musculoskeletal, and nervous system and as 
assessment for signs suggestive of a PIMMC. 
{}Targeted physical examination if indicated based on review of interim medical history. 


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^ Will be performed on all women of childbearing potential at screening (optional) and within 24 hours prior to each study vaccination and results must be negative 
and known prior to each study vaccination. 
Ψ  Subjects who do not receive the second study vaccination will continue with follow-up safety assessments (may be conducted by phone call) rather than in person 
continuing through approximately 12 months after their first study vaccination. These subjects will also be encouraged to provide a venous blood sample for anti-
viral antibody assays at approximately 21 days after their first study vaccination 
4 For subjects who have consented to collection of serum for future use either by signing an ICF 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 ICF allows the option to choose that option. 
& Inclusive of reactogenicity assessments performed on the day of each study vaccination through 7 days after each study vaccination. 
 
5 All concomitant medications taken within 60 days prior to signing the ICF will be reviewed with subjects.  Medications reported in the eCRF are limited to those taken within 30 
days prior to the first study vaccination through approximately 180 days after the last study vaccination, including receipt of any non-study influenza vaccine. 
6 Targeted physical examination may be done at Visit 01 if Visit 00, screening visit was conducted, and if indicated based on review of interim medical history.   
 
 
 


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APPENDIX B. LIST OF POTENTIALLY IMMUNE MEDIATED 
MEDICAL CONDITIONS 
[also known as Adverse Events of Special Interest (AESIs).  This list is not all inclusive]. 
 
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 rheumatica 
• 
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 
• 
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 (granulomatosis with 
polyangiitis), 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 
Others 
• 
Antiphospholipid syndrome 


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• 
Autoimmune hemolytic anemia 
• 
Autoimmune glomerulonephritis (including IgA nephropathy, glomerulonephritis rapidly 
progressive, membranous glomerulonephritis, membranoproliferative glomerulonephritis, 
and mesangioproliferative glomerulonephritis) 
• 
Autoimmune myocarditis/cardiomyopathy 
• 
Autoimmune thrombocytopenia 
• 
Goodpasture 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  
17-0076: A Phase II Study in Healthy Adults 18-64 Years Old to Assess the 
Safety, Reactogenicity and Immunogenicity of a Seqirus A/H7N9 
Inactivated Influenza Vaccine Administered Intramuscularly With or 
Without MF59® Adjuvant 
 
 
17-0076: NCT03682120 
 
Version 1.0 
 
DATE: 7 May 2020 
 
THIS COMMUNICATION IS PRIVILEGED AND CONFIDENTIAL  
 


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STUDY TITLE 
Protocol Number Code: 
DMID Protocol: 17-0076  
Development Phase: 
Phase II 
Products: 
Seqirus A/H7N9 Inactivated Influenza Vaccine  
Seqirus MF59® Adjuvant 
Form/Route: 
IM 
Indication Studied: 
Influenza A/H7N9 
Sponsor: 
Division of Microbiology and Infectious Diseases 
National Institute of Allergy and Infectious Diseases 
National Institutes of Health 
Clinical Trial Initiation Date: 
November 2, 2018 
Clinical Trial Completion Date: 
April 23, 2020 
 
Date of the Analysis Plan: 
May 7, 2020 
Version Number: 
Version 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. 
 


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TABLE OF CONTENTS 
STUDY TITLE ........................................................................................................................................... II 
LIST OF ABBREVIATIONS .................................................................................................................... VI 
1. 
PREFACE ............................................................................................................................................ 1 
2. 
INTRODUCTION ............................................................................................................................... 2 
2.1. 
Purpose of the Analyses ................................................................................................................ 2 
3. 
STUDY OBJECTIVES AND ENDPOINTS ....................................................................................... 3 
3.1. 
Study Objectives ........................................................................................................................... 3 
3.1.1. 
Primary ................................................................................................................................ 3 
3.1.2. 
Secondary ............................................................................................................................ 3 
3.1.3. 
Exploratory .......................................................................................................................... 3 
3.2. 
Endpoints ...................................................................................................................................... 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 ................................................................. 8 
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 .......................................................................................... 9 
4.5.1. 
Safety Variables .................................................................................................................. 9 
4.5.2. 
Immunogenicity Variables ................................................................................................ 10 
5. 
SAMPLE SIZE CONSIDERATIONS .............................................................................................. 11 
6. 
GENERAL STATISTICAL CONSIDERATIONS ........................................................................... 12 


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6.1. 
General Principles ....................................................................................................................... 12 
6.2. 
Timing of Analyses ..................................................................................................................... 12 
6.2.1. 
CSR ................................................................................................................................... 12 
6.3. 
Analysis Populations ................................................................................................................... 13 
6.3.1. 
Safety Population .............................................................................................................. 13 
6.3.2. 
Modified Intention-to-Treat (mITT) Population ............................................................... 13 
6.3.3. 
Per-Protocol Population .................................................................................................... 13 
6.4. 
Covariates and Subgroups ........................................................................................................... 14 
6.5. 
Missing Data ............................................................................................................................... 14 
6.6. 
Interim Analyses and Data Monitoring ....................................................................................... 14 
6.6.1. 
Interim Safety Review ....................................................................................................... 15 
6.6.2. 
Interim Immunogenicity Review....................................................................................... 15 
6.7. 
Multicenter Studies ..................................................................................................................... 15 
6.8. 
Multiple Comparisons/Multiplicity ............................................................................................. 15 
7. 
STUDY SUBJECTS .......................................................................................................................... 16 
7.1. 
Subject Disposition ..................................................................................................................... 16 
7.2. 
Protocol Deviations ..................................................................................................................... 16 
8. 
IMMUNOGENICITY EVALUATION ............................................................................................ 17 
8.1. 
Primary Immunogenicity Analysis ............................................................................................. 17 
8.2. 
Secondary Immunogenicity Analyses ......................................................................................... 17 
8.3. 
Exploratory Immunogenicity Analyses....................................................................................... 17 
8.3.1. 
Covariate Analysis ............................................................................................................ 17 
8.3.2. 
Regression Modeling......................................................................................................... 18 
8.3.3. 
Analysis of Heterologous Strain ....................................................................................... 18 
8.3.4. 
NA Serum Antibody Responses ........................................................................................ 19 
9. 
SAFETY EVALUATION ................................................................................................................. 20 
9.1. 
Demographic and Other Baseline Characteristics ....................................................................... 20 
9.1.1. 
Prior and Concurrent Illnesses and Medical Conditions ................................................... 20 
9.1.2. 
Prior and Concurrent Medications .................................................................................... 20 
9.2. 
Measurements of Treatment Compliance ................................................................................... 20 
9.3. 
Adverse Events ........................................................................................................................... 21 
9.3.1. 
Solicited Events and Symptoms ........................................................................................ 21 
9.3.2. 
Unsolicited Adverse Events .............................................................................................. 22 
9.4. 
Deaths, Serious Adverse Events and other Significant Adverse Events ..................................... 23 


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9.5. 
Pregnancies ................................................................................................................................. 23 
9.6. 
Clinical Laboratory Evaluations ................................................................................................. 23 
9.7. 
Vital Signs and Physical Evaluations .......................................................................................... 24 
9.8. 
Concomitant Medications ........................................................................................................... 24 
10. REPORTING CONVENTIONS ....................................................................................................... 25 
11. TECHNICAL DETAILS ................................................................................................................... 26 
12. SUMMARY OF CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED  
ANALYSES ...................................................................................................................................... 27 
13. REFERENCES .................................................................................................................................. 28 
14. APPENDICES ................................................................................................................................... 29 
APPENDIX 1. TABLE MOCK-UPS ........................................................................................................ 30 
APPENDIX 2. FIGURE MOCK-UPS ..................................................................................................... 114 
APPENDIX 3. LISTINGS MOCK-UPS ................................................................................................. 132 
 
 


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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 
DHHS 
U.S. Department of Health and Human Services 
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 
HAI 
Hemagglutination inhibition antibody 
Hgb 
Hemoglobin 
ICH 
International Conference on Harmonisation 
IIV 
Inactivated Influenza Vaccine 
IM 
Intramuscularly 
IRB 
Institutional Review Board 
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 
NIH 
National Institutes of Health 
NOCMC 
New Onset Chronic Medical Condition 


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


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1. 
PREFACE 
This Statistical Analysis Plan (SAP) for DMID Protocol 17-0076, “A Phase II Study in 
Healthy Adults 18-64 Years Old to Assess the Safety, Reactogenicity and Immunogenicity of 
a Seqirus A/H7N9 Inactivated Influenza Vaccine Administered Intramuscularly With or 
Without MF59 Adjuvant,” 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 final 
analyses included in the Clinical Study Report (CSR). Regarding the final analyses and CSR, 
this SAP follows the International Conference on Harmonisation of Technical Requirements 
for Registration of Pharmaceuticals for Human Use (ICH) Guidelines, as indicated in Topic 
E3 (Structure and Content of Clinical Study Reports), and more generally is consistent with 
Topic E8 (General Considerations for Clinical Trials) and Topic E9 (Statistical Principles for 
Clinical Trials). The structure and content of the SAP provides sufficient detail to meet the 
requirements identified by the FDA and ICH, while all work planned and reported for this 
SAP will follow internationally accepted guidelines published by the American Statistical 
Association and the Royal Statistical Society for statistical practice.  
This document contains four sections: (1) a review of the study design, (2) general statistical 
considerations, (3) comprehensive statistical analysis methods for immunogenicity and safety 
outcomes, and (4) a list of proposed TFLs. Following any protocol amendment, this SAP will 
be reviewed and revised (if needed) to address any changes in the protocol impacting 
analysis. Any deviation from the final SAP will be described and justified in the CSR. The 
reader of this SAP is encouraged to also review the study protocol for details on conduct of 
the study and the operational aspects of clinical assessments. 


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2. 
INTRODUCTION 
Since March of 2013 [1], avian influenza A/H7N9 viruses have continued to circulate in 
China causing discrete outbreaks (or waves) in humans with high mortality over the past 5 
years. By late 2016, a fifth wave of outbreaks was identified in China and as of May 18, 
2017, a total of 1,463 laboratory-confirmed human infections with avian influenza A/H7N9 
virus have been reported by the World Health Organization [2, 3]. Since the onset of the fifth 
wave of H7N9 outbreaks in October 2016, more human cases of H7N9 infection have been 
reported in China than any prior H7N9 epidemic wave [3]. The U.S. Department of Health 
and Human Services (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, 
DHHS 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, ages 18-64, the safety, 
reactogenicity, and immunogenicity of two doses of a monovalent inactivated influenza 
A/H7N9 virus vaccine administered IM at different dosages given with or without MF59 
adjuvant and to evaluate the potential of the dosage levels and adjuvant to enhance the 
immune response to A/H7N9 vaccine. The two doses of the A/H7N9 vaccine given with or 
without adjuvant will be administered approximately 21 days apart. 
2.1. 
Purpose of the Analyses 
These analyses will assess the safety and immunogenicity of two doses of A/H7N9 IIV 
administered IM with or without MF59 adjuvant approximately 21 days apart and will be 
included in the clinical study report.  


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3. 
STUDY OBJECTIVES AND ENDPOINTS 
3.1. 
Study Objectives 
3.1.1. 
Primary 
Safety: 
• To assess the safety and reactogenicity following receipt of two doses of 2017 
H7N9 IIV administered IM at different dosages approximately 21 days apart 
given with or without MF59 adjuvant. 
Immunogenicity: 
• To assess the serum hemagglutination inhibition (HAI) and neutralizing (Neut) 
antibody responses approximately 21 days following receipt of two doses of 2017 
H7N9 IIV administered IM at different dosages approximately 21 days apart with 
or without MF59 adjuvant. 
3.1.2. 
Secondary  
Safety: 
• To assess all unsolicited non-serious adverse events (AEs) following receipt of 
two doses of a 2017 H7N9 IIV administered IM at different dosages 
approximately 21 days apart with or without MF59 adjuvant  
• To assess medically-attended adverse events (MAAEs) including new-onset 
chronic medical conditions (NOCMCs), potentially immune-mediated medical 
conditions (PIMMCs), and all serious adverse events (SAEs) following receipt of 
two doses of a 2017 H7N9 IIV administered IM at different dosages 
approximately 21 days apart with or without MF59 adjuvant  
Immunogenicity: 
• To assess the serum HAI and Neut antibody responses approximately 7 and 21 
days following receipt of a single dose, and approximately 7 days following 
receipt of two doses of 2017 H7N9 IIV administered IM at different dosages 
approximately 21 days apart with or without MF59 adjuvant. 
3.1.3. 
Exploratory 
Immunogenicity: 
• To assess the effects of age, sex, body mass index, and prior receipt of seasonal 
influenza vaccine(s) on serum HAI and Neut antibody responses following receipt 
of two doses of a 2017 H7N9 IIV administered IM at different dosages 
approximately 21 days apart with or without MF59 adjuvant. 


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• To assess, in at least a subset of samples, the cross-reactivity of serum HAI and 
Neut antibody responses to antigenically drifted variants of influenza A/H7 
viruses following receipt of two doses of a 2017 H7N9 IIV administered IM at 
different dosages approximately 21 days apart with or without MF59 adjuvant.  
• To assess the durability of serum HAI and Neut antibody responses at 
approximately 180 days following receipt of two doses of 2017 H7N9 IIV 
administered IM at different dosages approximately 21 days apart with or without 
MF59 adjuvant.  
• To assess the neuraminidase (NA) content of the 2017 H7N9 IIV and determine 
the serum antibody responses to NA following receipt of 2017 H7N9 IIV. Note: 
analysis plans for this objective will be described in an addendum to this SAP 
once the NA assay has been selected. 
3.2. 
Endpoints 
3.2.1. 
Primary 
Safety: 
• Occurrence of study vaccine-related serious adverse events (SAEs) from the time 
of the first study vaccination through approximately 12 months after the last study 
vaccination. 
• Occurrence of solicited injection site and systemic reactogenicity events from the 
time of each study vaccination through 7 days after each study vaccination. 
• Occurrence of clinical safety laboratory adverse events from the time of each 
study vaccination through approximately 7 days after each study vaccination. 
Immunogenicity: 
• For HAI and Neut antibodies, percentage of subjects achieving seroconversion 
against the influenza 2017 H7N9 study vaccine strain (defined as either a pre-
vaccination titer <1:10 and a post-vaccination titer ≥1:40 or a pre-vaccination titer 
≥1:10 and a minimum four-fold rise in post-vaccination titer) at approximately 21 
days after the second study vaccination (Study Day 43). 
• For HAI and Neut antibodies, percentage of subjects achieving titer ≥1:40 against 
the influenza 2017 H7N9 study vaccine strain at approximately 21 days after the 
second study vaccination (Study Day 43). 
• Geometric Mean Titers (GMTs) of serum HAI and Neut antibodies against the 
influenza 2017 H7N9 vaccine strain at approximately 21 days after the second 
study vaccination (Study Day 43).  


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


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antigenically drifted variants of influenza A/H7 viruses at baseline and 
approximately 21 and 180 days after the second study vaccination (Study Day 43 
and 202). 
• For HAI and Neut antibodies, percentage of subjects achieving seroconversion, 
percentage with titer ≥1:40, and GMTs against the 2017 H7N9 study vaccine 
strain at approximately 180 days after the second study vaccination (Study Day 
202). 
• Percentage of subjects with detectable levels of serum N9 NA specific antibody 
elicited by 2017 H7N9 vaccination, and the correlation of the NA content of 2017 
H7N9 IIV with the elicited NA specific antibody responses at baseline and 
approximately 8 and 21 days after the first study vaccination (Study Day 1, 8 and 
22) and 8, 21 and 180 days after the second study vaccination (Study Day, 29, 43 
and 202). Note: analysis plans for this endpoint will be described in an addendum 
to this SAP once the NA assay has been selected. 
3.3. 
Study Definitions and Derived Variables 
For individual subjects, fold rise will be calculated as the ratio of: 
𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝−𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡
𝑝𝑝𝑝𝑝𝑝𝑝−𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡, where 
pre-vaccination value is always the result obtained at Day 1, prior to the priming vaccination. 
Seroconversion for HAI and Neut assays is defined as either a pre-vaccination titer < 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 [5]. 


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4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design and Plan 
The protocol follows a Phase II randomized, double blind study design enrolling 371 males 
and non-pregnant females, 18-64 years of age who are in good health as determined by 
medical history and physical examination, and meet all eligibility criteria, including 
erythrocyte sedimentation rate (ESR), hematology, and biochemistry parameters within 
acceptable range, and negative urine or serum pregnancy test (for females). This clinical trial 
is designed to assess the safety, reactogenicity, and immunogenicity of a monovalent 
inactivated influenza A/H7N9 virus vaccine at different dosages (3.75 mcg, 7.5 mcg, 15 mcg 
of HA per dose) with MF59 adjuvant, or at a dosage of 15 mcg per dose without adjuvant.  
In this trial, subjects will be randomly assigned to 1 of 4 study groups with allocation 2:2:2:1 
(see Table 1) stratified by site and prior receipt of at least one of the 2017-2018 and/or 2018-
2019 seasonal influenza vaccine. The same dosage of vaccine with or without the same 
adjuvant will be given to subjects at both of their first and second study vaccinations. All 
study vaccinations will be administered IM approximately 21 days apart. Subjects assigned 
to study arm 1 will receive 3.75mcg A/H7N9 IIV and MF59, subjects assigned to study arm 
2 will receive 7.5mcg A/H7N9 IIV and MF59, subjects assigned to study arm 3 will receive 
15mcg A/H7N9 IIV and MF59, and subjects assigned to study arm 4 will receive 15mcg 
A/H7N9 unadjuvanted.  
Reactogenicity will be measured by the occurrence of solicited injection site and systemic 
reactions from the time of each study vaccination through 7 days after each study 
vaccination. Unsolicited non-serious AEs will be collected from the time of each study 
vaccination through approximately 21 days after each study vaccination. SAEs, MAAEs, 
including NOCMCs, and PIMMCs, will be collected from the time of the first study 
vaccination through approximately 12 months after the last study vaccination. Clinical 
laboratory evaluations for safety will be performed on venous blood collected prior to each 
study vaccination and approximately 7 days after each study vaccination. 
Immunogenicity testing will include performing HAI and Neut antibody assays against the 
2017 A/H7N9 vaccine virus and drifted variants of the A/H7N9 virus on serum samples 
obtained immediately prior to each study vaccination (Days 1 and approximately Day 22), 
approximately 7 days after each study vaccination (Days 8 and 29), and approximately 21 
and 180 days after the second study vaccination (Days 43 and 202). 
Novel methods for identifying and assessing alternative correlates of protection against 
influenza infection are needed. To assess the NA specific antibody response to vaccination, it 
is first necessary to determine the NA content of inactivated influenza vaccine; this assay is 
under development. If successful, the NA content in a dosage specific manner can be 
correlated to the N9 NA-specific antibody responses elicited by the 2017 H7N9 IIV. 


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4.2. 
Discussion of Study Design, Including the Choice of Control 
Groups 
This study uses a dose comparison concurrent control design. All subjects receive the same 
study product (A/H7N9 IIV) with differing dosages with or without MF59 adjuvant. 
4.3. 
Selection of Study Population 
The study population for this clinical trial is 371 males and non-pregnant females, 18-64 
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 Vaccine Trial and Evaluation Unit 
(VTEU) sites that have substantial experience conducting large influenza vaccine studies. 
4.4. 
Treatments 
4.4.1. 
Treatments Administered  
A/H7N9 Vaccine and MF59 Adjuvant will be administered. 
4.4.2. 
Identity of Investigational Product 
See the study protocol for details of study product formulation. 
4.4.3. 
Method of Assigning Subjects to Treatment Groups (Randomization) 
Enrollment/randomization will be performed through the enrollment module in the electronic 
data capture system maintained by the Statistical and Data Coordinating Center (SDCC).  
Eligible subjects will be stratified by clinical site and prior receipt of at least one of the 2017-
2018 and/or 2018-2019 seasonal influenza vaccines then randomly assigned with allocation 
(2:2:2:1) to one of 4 study arms indicated in Table 1. The treatment sequence was generated 
using permuted block randomization to provide an approximately balanced allocation to the 
study arms during the study. 
4.4.4. 
Selection of Doses in the Study 
Participants in this study are to receive two A/H7N9 vaccinations at HA doses of 3.75, 7.5, or 
15 mcg with MF59 adjuvant, or at a HA dose of 15 mcg without adjuvant. The 3.75, 7.5, or 
15 mcg with MF59 doses are selected to evaluate safety and immunogenicity of antigen 
sparing dose strategies.  Per FDA Guidance [5], the 15mcg non-adjuvanted dose was selected 
to compare immune response with the 15 mcg adjuvanted vaccine. 
4.4.5. 
Selection and Timing of Dose for Each Subject 
Each subject is to be randomly assigned to a study group which will define the A/H7N9 
vaccine dose and receipt of adjuvant for both planned study vaccinations. The first 
vaccination takes place on the day of randomization, and the second vaccination takes place 
approximately 21 days after the first vaccination (protocol defined window of 21-28 days 
post first vaccination). 


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4.4.6. 
Blinding 
This trial is double-blinded; subjects, investigators, study personnel performing any study-
related assessments following study vaccine administration, and laboratory personnel 
performing antibody assays are blinded to dosage within study vaccination schedule. 
The randomization scheme was generated by the SDCC and provided to unblinded study 
personnel (i.e., pharmacists performing study vaccination preparations and unblinded study 
vaccine administrators) at the participating VTEU sites who will not be not involved in 
study-related assessments or have subject contact for data collection following study vaccine 
administration. 
The Data and Safety Monitoring Board (DSMB) may receive data in aggregate and presented 
by group. The DSMB may also be provided with expected and observed rates of the expected 
AEs in an unblinded fashion, and may request treatment assignment be unblinded for an 
individual subject if required for safety assessment. The DSMB will review grouped and 
unblinded data in the closed session only. 
4.4.7. 
Prior and Concomitant Therapy 
Administration of any medications, therapies, or vaccines (including prescription and over-
the-counter drugs as well as herbals, vitamins, and supplements) from 60 days prior to study 
vaccination through 180 days post final vaccination will be solicited from the participant 
during screening, enrollment, and follow-up. Any reported prior therapies from up to 30 days 
prior to vaccination through 180 days post final vaccination will be recorded in the 
appropriate data collection form.  
Prior receipt of a licensed seasonal influenza vaccine over the current (2018-2019) and 
previous two seasons (2016-2017 and 2017-2018) is not exclusionary as long as it has been 
administered within the allowable window (protocol Section 5.1.2). 
Use of concomitant medications is allowed prior to and during the trial with the exception of 
medications and therapies that might interfere with the evaluation of the investigational 
product. Medications in this category include the prohibited medication per the Subject 
Exclusion Criteria (protocol Section 5.1.2). In addition, the site principal investigator or 
appropriate sub-investigator may identify other medications that should not be used due to a 
risk to subject safety or assessment of reactogenicity and immunogenicity. 
4.4.8. 
Treatment Compliance 
All subjects are to receive two doses of study product administered in the clinic. 
4.5. 
Immunogenicity and Safety Variables 
See Table 2 and Table 3 for schedule of study procedures. 
4.5.1. 
Safety Variables 
Safety will be assessed by the frequency and severity of: 


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1. SAEs occurring from the time of the first study vaccination through approximately 12 
months after the last study vaccination. 
2. Solicited AEs – reactogenicity events occurring from the time of each study 
vaccination through 7 days after each study vaccination: 
a) Injection site reactions including pruritus, ecchymosis, erythema, 
induration/swelling, pain, and tenderness. 
b) Systemic reactions including fever, feverishness, fatigue, malaise, myalgia, 
arthralgia, headache, and nausea. 
3. Clinical safety laboratory AEs occurring from the time of each study vaccination 
through approximately 7 days after each study vaccination. Parameters to be 
evaluated include 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 9, Table 10, Table 11, and Table 12. 
4.5.2. 
Immunogenicity Variables 
Individual HAI and Neut results will be reported by the central immunology laboratory for 
the homologous vaccine strain, A/Hong Kong/125/2017 (H7N9), and heterologous strains, 
A/Shanghai/2/2013 (H7N9) and A/Guangdong/17SF003/2016xPR8/17SF003/2016xPR8 
(H7N9). Assay results are reported as a reciprocal titer with values of 10*2k, where k=0, 1, 2, 
etc. The lower limit of detection for the HAI and Neut assays is 1:10; values below the limit 
of detection are imputed for analysis as one-half the limit of detection (10/2 = 5). For 
analysis, the geometric mean (calculated on natural log scale) of repeated results for each 
sample will be computed and used as the response for all subsequent calculations. The 
variation arising from multiple measurements for an individual at a single time point is not 
used in subsequent calculations. See Section 3.3 for definitions of derived variables for the 
analysis of HAI and Neut data. 
To assess the Neuraminidase Antigen (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. An 
addendum to the SAP will be generated to outline the planned analyses when assay 
development is complete.  
All immunogenicity data will be uploaded into the SDCC’s electronic data capture system. 


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5. 
SAMPLE SIZE CONSIDERATIONS 
This study is planned to enroll 106 subjects in each adjuvanted study arm and 53 subjects in 
the unadjuvanted study arm. Randomization at each site will be stratified by prior receipt of 
season influenza vaccines, however there is no enrollment target for these strata. The sample 
size for this study was selected to obtain preliminary estimates in a time critical manner. 
While this study is not designed to test any specific null hypothesis, the following tables 
illustrate the precision and power that is available for select estimates and comparisons of 
interest. 
Table 4 indicates the probability of observing one or more safety events, such as solicited 
injection site or systemic reactogenicity events or an unsolicited non-serious AE of a 
particular type for a single study arm (N = 53, 106) and for all subjects receiving adjuvanted 
vaccine (N = 318). 
Binomial confidence intervals (CI) are widest (have the least precision) when the response 
rate is 50%. Table 5 is presented to indicate the worst-case scenario for precision of observed 
exact (Clopper-Pearson) binomial confidence intervals. 
Table 6 illustrates the minimum detectable differences in the proportion of subjects 
responding (e.g., attaining seroconversion or a titer ≥1:40) between two adjuvanted study 
arms within each stratum using a two-sided Likelihood Ratio Test and alpha = 0.05. 
Power calculations assume n=100 per adjuvanted group and n=50 for the unadjuvanted 
group. Based on previous DMID A/H7N9 trials it is expected 5% of enrolled subjects in this 
stratum may be excluded from analysis of the primary endpoint. In the event that only 100 
subjects are actually enrolled in a study arm, the small dropout rates anticipated would have a 
minimal impact on the calculations presented in Table 7.  
Per FDA guidance [5,6], for differences in HAI antibody response rates, the lower 
confidence limit on the appropriate point estimate excluding equality (i.e., 0 for the 
difference parameter) may be sufficient to demonstrate the added value of the adjuvant. 
Table 7 shows the lower bound of the 95% confidence interval for the difference in the 
proportion of responders between the adjuvanted and unadjuvanted arms (e.g. 15 mcg + 
MF59 minus 15 mcg unadjuvanted) assuming the proportion of responders in the 
unadjuvanted arm is 0.10 and considering a range for the proportion of responders in the 
adjuvanted arm ranges from 0.50 to 0.90.  


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6. 
GENERAL STATISTICAL CONSIDERATIONS 
6.1. 
General Principles 
All continuous variables will be summarized using the following descriptive statistics: n 
(non-missing sample size), mean, standard deviation, median, maximum and minimum. The 
frequency and percentages (based on the non-missing sample size) of observed levels will be 
reported for all categorical measures. In general, all data will be listed, sorted by site, study 
arm and subject, and when appropriate by visit number within subject. All summary tables 
will be structured with a column for each study arm in the following order: 
• Arm 1: 3.75 mcg A/H7N9 + MF59 
• Arm 2: 7.5 mcg A/H7N9 + MF59 
• Arm 3: 15 mcg A/H7N9 + MF59 
• Arm 4: 15 mcg A/H7N9 
All tables will be annotated with the total population size relevant to that table/arm, including 
any missing observations. 
6.2. 
Timing of Analyses 
6.2.1. 
CSR 
Once the last subject completes the visit that occurs approximately at Day 387, the clinical 
database will be cleaned, monitored, and locked. The CSR will be completed when all safety 
data through Day 387 and all humoral immunogenicity data through Day 202 are completed 
and uploaded.  
Upon receipt of humoral immunogenicity against homologous influenza A/Hong 
Kong/125/2017 (H7N9) virus through Day 202 and non-clinical data lock, a subset of 
predefined “topline tables” will be generated by the SDCC concurrently with CSR 
generation. These tables will include summaries of safety and immunogenicity data and will 
represent the final analyses of primary endpoints; as such no p-value adjustment is required. 
These analyses may be made available to the sponsor for planning subsequent trials and to 
the lead PI for publication. Tables to be included in the topline set are indicated with the 
symbol * in the title. 
Analysis of exploratory immunogenicity endpoints may be performed and released as the 
data are available from the research laboratory. Any such analyses would be considered the 
final analysis for the endpoint and included in the CSR. Additional exploratory 
immunogenicity endpoint data not available at the time of CSR preparation may be included 
in an addendum to the CSR. 


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6.3. 
Analysis Populations 
6.3.1. 
Safety Population 
The Safety Analysis population includes all subjects who received at least one study 
vaccination. 
6.3.2. 
Modified Intention-to-Treat (mITT) Population 
The modified intent-to-treat (mITT) population includes all subjects who received at least 
one study vaccination and contributed both pre- and at least one post-study vaccination 
venous blood samples for immunogenicity testing (HAI or Neut antibody assays) for which 
valid results were reported. For analyses using the mITT population, subjects will be grouped 
based on randomized study arm.  
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 study vaccination not received, 
o Second study vaccination received out of window, 
o Receipt of non-study licensed live vaccine within 30 days before or after each 
study vaccination, 
o Receipt of non-study licensed inactivated vaccine within 14 days before or after 
each study vaccination, 
o Receipt of immunosuppressive therapy (e.g., corticosteroids) within 30 days 
before or after each study vaccination. 
• Data from any visit that occurs out of window: 
o Visit 3 data collected before 6 days or after 10 days post first study vaccination 
o Visit 4 data collected before 20 days or after 29 days post first study vaccination. 
o Visit 6 data collected before 6 days or after 10 days post second study vaccination. 
o For subjects who did not receive the second study vaccination, visit 6 data 
collected before 27 days or after 31 days post first study vaccination. 
o Visit 7 data collected before 20 days or after 29 days post second study vaccination. 
o For subjects who did not receive the second study vaccination, visit 7 data 
collected before 41 days or after 50 days post first study vaccination. 


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o Visit 10 data collected before 165 days or after 195 days post second study 
vaccination. 
o For subjects who did not receive the second study vaccination, visit 10 data 
collected before 200 days or after 216 days post first study vaccination. 
For analyses using the PP population, subjects will be grouped based on study vaccinations 
received. 
6.4. 
Covariates and Subgroups 
As a protocol defined exploratory analysis, HAI antibody response following the second 
vaccination will be summarized stratified by the following covariates: age (categorical: 18-
34, 35-49, 50-64), sex (male, female), body mass index (<30, ≥30), and prior receipt of 
seasonal influenza vaccine(s) (receipt of 2017-2018 or 2018-2019, or receipt of neither), and 
these covariates will be considered in statistical modeling as described in Section 8.3. As 
these analyses are exploratory the study was not powered for any subgroup analyses.  
6.5. 
Missing Data 
All attempts will be made to collect all data Per-Protocol. As missing data are expected to be 
minimal, no imputation will be performed for missing values. Any data point that appears to 
be erroneous or inexplicable based on clinical judgment will be investigated as a possible 
outlier. If data points are identified as outliers, sensitivity analyses will be performed to 
examine the impact of including or excluding the outliers. Any substantive differences in 
these analyses will be reported. 
6.6. 
Interim Analyses and Data Monitoring 
Interim analyses will only be used to terminate this trial in the event that unanticipated safety 
events deemed to be of sufficient concern require such action by the sponsor. These 
assessments will not be made on the basis of testing a formal statistical hypothesis; therefore, 
p-value adjustment will not be made to any analyses. A DSMB will be convened by DMID 
to review study progress and participant, clinical, safety, and reactogenicity and 
immunogenicity data. 
Clinical, safety, and reactogenicity data through approximately 180 days after the second 
study vaccination will represent the primary clinical database for this trial. Once the last 
subject completes the visit that occurs approximately 180 days after second study vaccination 
and all HAI and Neut results are received, a “topline” subset of the immunogenicity and 
safety tables will be provided to DMID on an expedited timeline.  These analyses may be 
made available to the sponsor for planning subsequent trials and to the lead PI for publication 
and will be considered the final analysis of these data. 
Emergent public health needs may dictate additional interim safety, reactogenicity, and/or 
immunogenicity analyses be performed on available information at any time during the trial. 
If this occurs, immunogenicity data will be analyzed as results are available from the central 
immunogenicity laboratory. 


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6.6.1. 
Interim Safety Review 
An interim safety review may include enrollment and demographic information, medical 
history, concomitant medications, physical assessments, clinical laboratory values, dosing 
compliance, and solicited and unsolicited AE/SAEs. Additional data may be requested by the 
DSMB, and interim statistical reports may be generated as deemed necessary and appropriate 
by DMID. The DSMB may receive data in aggregate and presented by study arm. The 
DSMB may also be provided with expected and observed rates of the expected AEs in an 
unblinded fashion and may request the treatment assignment be unblinded for an individual 
subject if required for safety assessment. The DSMB will review grouped and unblinded data 
in the closed session only. The DSMB will meet and review this data at scheduled time 
points or ad hoc as needed during this trial as defined in the DSMB charter. As an outcome 
of each review/meeting, the DSMB will make a recommendation as to the advisability of 
proceeding with study vaccinations (as applicable), and to continue, modify, or terminate this 
trial. Summaries prepared for the DSMB are defined separately in a report shell reviewed and 
approved by the DSMB. 
Additionally, this trial will be monitored to determine if any of the halting rules described in 
Protocol Section 9.5 are met. 
6.6.2. 
Interim Immunogenicity Review 
Clinical, safety, and reactogenicity data through approximately 180 days after the second 
study vaccination will represent the primary clinical database for this trial. Once the last 
subject completes the visit that occurs approximately 180 days after second study vaccination 
and all HAI and Neut results are received, a “topline” subset of the immunogenicity and 
safety tables will be provided to DMID on an expedited timeline.  These analyses may be 
made available to the sponsor for planning subsequent trials and to the lead PI for publication 
and will be considered the final analysis of these data. 
Should emergent public health needs dictate interim immunogenicity review, immune 
responses will be summarized in terms of strain-specific 2017 A/H7N9 HAI and Neut 
antibody titers. Any immunogenicity reports would be provided by the SDCC to the DMID 
Scientific Lead and CPM, and the DSMB. Reports would include data summarized by 
treatment arm. 
6.7. 
Multicenter Studies 
Although randomization was stratified by site, data will be pooled across all clinical sites for 
all analyses. Center effects are not anticipated because the sites are using standardized 
procedures for vaccination and assessment of solicited and unsolicited AEs, and the study 
relies on a central laboratory for immunogenicity assessments. 
6.8. 
Multiple Comparisons/Multiplicity 
This study was designed to obtain preliminary estimates of safety and immune response to 
the A/H7N9 vaccination in healthy adults. The study was not designed to test any specific 
null hypothesis, and as such no adjustment for multiple comparisons will be performed. 


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7. 
STUDY SUBJECTS 
7.1. 
Subject Disposition 
Table 13 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 
study arm are presented in Table 14. 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 study arm in Table 15. The table 
will show the total number of subjects screened, randomized, receiving the first study 
vaccination, receiving the second study vaccination, completing the blood draw for the 
primary immunogenicity endpoints, and completing the last visit. 
A flowchart showing the disposition of study subjects, adapted from the CONSORT 
Statement [4] will be included and will present the number of subjects screened, randomized, 
lost to follow up, and analyzed, by study arm (see 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, study arm, and age stratum for all enrolled subjects in Table 8. 
Major deviations that will be reviewed for possible exclusion of immunogenicity results from 
the PP population include deviations related to eligibility/enrollment, 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 
Analysis of all immune responses will be conducted using the PP population. In addition, 
primary endpoint analyses will be conducted with the mITT population. Immune responses 
in terms of strain-specific A/H7N9 HAI and Neut antibody titers will be summarized by 
study arm at each time point. Descriptive summary statistics will be provided for all assays 
and time points including number of subjects with non-missing results, percentage of 
subjects with titers ≥1:40, percentage of subjects achieving seroconversion, and GMTs along 
with corresponding 95% CI. Exact confidence intervals will be presented for proportional 
endpoints. Summaries of primary and secondary immunogenicity endpoints are presented in 
Table 23, Table 24, Table 25, and Table 26. 
Reverse cumulative distribution (RCD) curves will be presented for post-vaccination HAI 
and Neut antibody titers. Plots for each assay will be generated with 4 panels (8 days post 
vaccination 1, 21 days post vaccination 1, 8 days post vaccination 2, 21 days post vaccination 
2, and 180 days post vaccination 2), and separate curves within each panel for each study 
arm, as shown in Figure 2, Figure 3, Figure 4, and Figure 5. 
Figures depicting the HAI and Neut GMT over time will also be presented as shown in 
Figure 6, Figure 7, Figure 8, and Figure 9. 
The spearman correlation between HAI and Neut antibody titers will be calculated at each 
time point over all groups. The correlation will be depicted in scatter plots as Figure 10 and 
Figure 11. 
Individual HAI and Neut assay results will be provided in Listing 8 and Listing 9. 
8.1. 
Primary Immunogenicity Analysis 
The primary immunogenicity endpoints HAI and Neut seroconversion, percentage of 
subjects with titer ≥1:40, and GMTs against the homologous A/H7N9 vaccine strain 21 days 
after the second vaccination will be summarized as described above. Regression modelling of 
seroconversion and log titers is planned as described in Section 8.3.2.  
8.2. 
Secondary Immunogenicity Analyses 
The secondary immunogenicity endpoints HAI and Neut seroconversion, percentage of 
subjects with titer ≥40, and GMTs against the homologous A/H7N9 vaccine strain 8 and 21 
days after the first vaccination and 8 days after the second vaccination will be summarized as 
described above. No formal hypothesis testing is planned. 
8.3. 
Exploratory Immunogenicity Analyses 
Immunogenicity data summaries and analysis for exploratory endpoints will be presented for 
the PP populations. 
8.3.1. 
Covariate Analysis 
As an exploratory analysis, seroconversion and GMT of serum antibody for both HAI and 
Neut at 21 and 180 days after second vaccination will be summarized by study arm stratified 


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by age (categorized as those subjects ages 18-34, 35-49, 50-64) in Table 27, Table 28, 
Table 29, and Table 30, by sex in Table 31, Table 32, Table 33, and Table 34 by BMI in 
Table 35, Table 36, Table 37, and Table 38, and by prior receipt of seasonal influenza 
vaccines in Table 39, Table 40, Table 41, and Table 42. These stratified summaries will be 
presented for the PP population. It is anticipated that subjects will have little to no pre-
existing antibody at baseline, so seroconversion and titer ≥40 endpoints will be similar. 
8.3.2. 
Regression Modeling 
Logistic and multivariate linear regression will be utilized to test for the effects of the HA 
antigen dose and the MF59 adjuvant on seroconversion and GMT, respectively, for the PP 
population. Similar models will be fit for HAI and Neut Antibodies. Separate models will be 
fit for data from Day 21 post dose 2 and Day 180 post dose 2.  
Logistic regression will be fit to examine the relationship of HAI seroconversion at 21 days 
after the 2nd study vaccination with study arm. If the available titer data meets the required 
assumptions of normality after log transformation, multiple linear regression will be fit to 
examine the relationship of log transformed titers at 21 days after the 2nd study vaccination 
with study arm. Both models will be fit with and without adjustment for the following 
covariates (Z): age category (19-34 years, 35-49 years, 50-64 years), sex (female, male), BMI 
(<30, ≥30), and prior receipt of seasonal influenza vaccine (none in past 2 seasons, at least 
once in past 2 seasons). Modeling assumptions will be checked using standard diagnostic 
methods (e.g., using the INFLUENCE option in PROC LOGISTIC or PROC GLM). 
Parameter estimates and odds ratio estimates for the logistic models will be presented in 
Table 43, Table 44, Table 45, Table 46, Table 47, Table 48, Table 49, and Table 50. 
Parameter estimates for the multiple linear regression models will be presented in Table 51, 
Table 52, Table 53, Table 54, Table 55, Table 56, Table 57, and Table 58. 
Model 1A: Logistic Regression (without covariate adjustment): 
𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙[𝑃𝑃(𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠)] = 𝛽𝛽0 + 𝛽𝛽1 × 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 𝐴𝐴𝐴𝐴𝐴𝐴+ 𝜀𝜀 
Model 1B: Logistic Regression (with covariate adjustment): 
𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙[𝑃𝑃(𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠)] = 𝛽𝛽0 + 𝛽𝛽1 × 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 𝐴𝐴𝐴𝐴𝐴𝐴+ 𝛽𝛽2 × 𝑍𝑍+ 𝜀𝜀 
Model 2A: Multiple Linear Regression (without covariate adjustment): 
𝑙𝑙𝑜𝑜𝑜𝑜(𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡) = 𝛽𝛽0 + 𝛽𝛽1 × 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 𝐴𝐴𝐴𝐴𝐴𝐴+ 𝜀𝜀 
Model 2B: Multiple Linear Regression (with covariate adjustment): 
𝑙𝑙𝑙𝑙𝑙𝑙(𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡) = 𝛽𝛽0 + 𝛽𝛽1 × 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 𝐴𝐴𝐴𝐴𝐴𝐴+ 𝛽𝛽2 × 𝑍𝑍+ 𝜀𝜀 
Subjects missing data for one or more covariates will be excluded from Models 1B and 2B. 
8.3.3. 
Analysis of Heterologous Strain 
HAI and Neut antibody responses against antigenically drifted variants of influenza A/H7 
viruses including A/Shanghai/2/2013 and A/Guangdong/17SF003/2016xPR8  will be 
summarized for the Per-Protocol population as described in Section 8 and presented in 


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Table 59, Table 60, Table 61, Table 62, Figure 12, Figure 13, Figure 14, Figure 15, 
Figure 16, Figure 17, Figure 18, and Figure 19. A scatter plot of the correlation between HAI 
and Neut antibody responses for each of the drifted strains will be presented in Figure 20 , 
Figure 21, Figure 22, and Figure 23.  A scatter plot of the correlation between response to the 
vaccine strain and each heterologous strain will be presented in Figure 24 and Figure 25. No 
formal hypothesis testing or modeling for the exploratory analysis of heterologous strains is 
planned.  
8.3.4. 
NA Serum Antibody Responses 
Descriptions of the NA assays and planned analyses will be described in an addendum to this 
SAP. 


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9. 
SAFETY EVALUATION 
All summaries and analysis of safety data will be presented for the Safety Analysis 
Population. Safety summaries will be presented overall and grouped by study arm overall and 
by age stratum. 
Continuous variables will be summarized using the following descriptive statistics: n (non-
missing sample size), mean, standard deviation, median, maximum and minimum. All 
categorical measures will be summarized by the frequency and percentages of observed 
levels. The denominator for the percentages may be based on the number of non-missing 
observations for an assessment or based on the number of subjects in a population. This will 
be described for each table. 
9.1. 
Demographic and Other Baseline Characteristics 
Summaries of age, sex, ethnicity, race, BMI, and prior receipt of seasonal influenza vaccine 
will be presented by site in Table 18 and Table 19 and by study arm overall in Table 20 and 
Table 21. Age will be summarized as a continuous variable as well as by strata categories. 
Ethnicity is categorized as Hispanic or Latino, or not Hispanic and not Latino. In accordance 
with NIH reporting policy, subjects may self-designate as belonging to more than one race or 
may refuse to identify a race, the latter reflected in the electronic case report form (eCRF) as 
“No” to each racial option. BMI will be summarized as a continuous as well as categorical 
variable, categorized as (<30, ≥30). Self-reported history of prior receipt of seasonal 
influenza vaccine will be categorized as follows: 2017-2018, 2018-2019, receipt of none, or 
unknown. Demographic information for individual subjects will be provided in Listing 6. 
9.1.1. 
Prior and Concurrent Illnesses and Medical Conditions 
All current illnesses and past or pre-existing medical conditions will be coded using Medical 
Dictionary for Regulatory Activities (MedDRA®) version 20.0 or higher. 
Summaries of subjects’ prior and concurrent medical conditions will be presented by study 
arm in Table 22. 
Individual subject listings will be presented for all reported medical history including prior 
and concurrent medical conditions in Listing 7. 
9.1.2. 
Prior and 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 study arm for the Safety population in Table 108. 
A listing of concomitant medications will be presented in Listing 17.  
9.2. 
Measurements of Treatment Compliance 
All subjects are to receive 2 study vaccinations administered in the clinic. The number of 
study vaccinations administered to subjects will be presented by study arm and by site, 
overall in Table 16 and Table 17 and as part of the subject disposition in Table 15.  


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Listing 1 presents subjects who received investigational product with randomized study arm 
and study product received for each vaccination. 
9.3. 
Adverse Events 
A summary of all adverse events is provided in Table 63. A summary of those events that 
occurred in ≥5% of subjects in any treatment group is provided in Table 64. 
9.3.1. 
Solicited Events and Symptoms 
Systemic solicited adverse events were collected pre-vaccination, and systemic and injection 
site solicited adverse events were collected at-least 20 minutes post-vaccination and then 
daily for 7 days after each vaccination and graded on a scale of 0 (absent), 1 (mild),  
2 (moderate) and 3 (severe). Systemic events include fever, feverishness, fatigue, malaise, 
myalgia, arthralgia, headache, and nausea. The grading scale for systemic events, including 
quantitative grading for fever, is included in Table 10. Injection site 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 9. 
When calculating the incidence of solicited events, each subject will be counted once at the 
highest severity following the applicable vaccination, and any repetitions will be ignored. For 
summaries presented separately for each vaccination, the denominator for percentages will be 
the number of subjects who received the respective vaccination with non-missing data for the 
event summarized. For summaries over all vaccinations the denominator will be the number 
of subjects who received at least one vaccination with non-missing data for the event 
summarized. 
The number and percentage of subjects reporting at least one solicited adverse event of any 
severity will be summarized for each solicited symptom, any systemic symptom, any 
injection site 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 in Table 65, Table 66, 
and Table 67. Logistic regression models will be fit to estimate the effect of study arm on the 
probability of reporting any injection site event or reporting any systemic event in Table 68 
and Table 69. If statistically significant effects are observed in the model for local events or 
systemic events, then additional models will be fit for each individual event of that type. 
𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙[𝑃𝑃(𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸)] = 𝛽𝛽0 + 𝛽𝛽1 × 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 𝐴𝐴𝐴𝐴𝐴𝐴+ 𝜀𝜀, 
For each systemic and injection site event, any systemic event, any injection site event, and 
any solicited event, the maximum severity over 7 days after each vaccination will be 
summarized for the Safety population. The number and percentage of subjects reporting each 
event will be summarized by the maximum severity and treatment group overall and by age 
stratum, separately for each vaccination and over all vaccinations. For each event the 
denominator is the number of subjects who received the applicable vaccination with non-
missing data for the specific event. The 95% CI calculated using Clopper-Pearson 


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methodology from a binomial distribution (SAS Proc Freq with a binomial option) will be 
presented in Table 70, Table 71, and Table 72. 
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 as summary in 
Table 73, Table 74, and Table 75 and graphically in a bar chart in Figure 26 and Figure 27. A 
comparison of the event rate for each treatment group between vaccination 1 and vaccination 
2 will be presented, including p-values from McNemar’s test performed over all subjects for 
injection site and systemic symptoms in Table 76 and Table 77. 
Systemic and injection site 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 in Table 78. 
The following summaries for unsolicited AEs will be presented by MedDRA system organ 
class, preferred term, and study arm: 
• Incidence of AEs by severity and relationship to study product in Table 79; 
• Incidence of non-serious, related AEs by severity in Table 80; 
• Incidence of AEs over time (Days 1-8, Days 9-22 post each study vaccination) in 
Table 81; 
• Incidence of non-serious, related AEs over time (Days 1-8, Days 9-22 post each 
study vaccination) in Table 82 – 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) in Table 83; 
• Subject listing of non-serious AEs of moderate or greater severity in Table 87;  
• Bar chart displaying total frequency of AEs by severity and MedDRA system 
organ class, Study arm, and Age Stratum in Figure 28; 


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• Bar chart displaying incidence of AEs by severity and MedDRA system organ 
class, Study arm, and Age Stratum in Figure 29; 
• Bar chart displaying total frequency and incidence of AEs by relationship to study 
product and MedDRA system organ class and study arm in Figure 30 and 
Figure 31. 
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 in Table 84; 
• Potentially Immune-Mediated Medical Conditions in Table 85; 
• New Onset Chronic Medical Conditions in Table 86; 
A listing of all reported AEs by subject will be presented in Listing 11, sorted by Study arm, 
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. 
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 12. 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 study arm will be presented 
in Table 88, Table 89, Table 90, Table 91, Table 92, Table 93, and Table 94. Descriptive 
statistics including mean, standard deviation, median, minimum and maximum values by 
study day will be summarized for each parameter and for the change from baseline for each 
parameter in Table 95, Table 96, Table 97, Table 98, Table 99, and Table 100.  Box plots 
illustrating the change from baseline for each laboratory parameter will be presented in 
Figure 25, Figure 26, Figure 27, Figure 28, Figure 29, and Figure 30. Subject visits with 


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abnormal laboratory results, Grade 1 severity or higher, will be presented in Table 101 and 
Table 102 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 
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 11. Summaries of vital signs by maximum severity will be tabulated by 
visit and study arm in Table 103, Table 104, Table 105, Table 106, and Table 107. A listing 
of vital signs will be presented in Listing 15. 
Targeted physical examinations will be performed, if indicated, based on a subject’s medical 
history. A listing of physical exam findings will be presented (Listing 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, study 
arm for the Safety population (Table 108). 
 


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


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


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


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


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14. 
APPENDICES 
Table, figure, and listing shells are presented in Appendices 1, 2, and 3. Tables and figures 
included in the topline set are indicated by *. 
 
 


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APPENDIX 1. TABLE MOCK-UPS 
LIST OF TABLES 
Table 1: 
Study Design .............................................................................................................. 40 
Table 2: 
Schedule of Study Procedures – Vaccination Period ................................................. 41 
Table 3: 
Schedule of Study Procedures - Follow-Up Period (Including early termination and 
unscheduled visits) ..................................................................................................... 43 
Table 4: 
Power (%) to Detect Safety Events ............................................................................ 45 
Table 5: 
Precisions of Binomial Confidence Intervals ............................................................. 45 
Table 6: 
Minimum Detectable Difference in Proportion Responders with 80% Power .......... 45 
Table 7: 
Lower Confidence Bound for Difference in Proportion of Responders  Between 
Adjuvanted (N = 100) and Unadjuvanted (N = 50) Arms, 18-64 Years Stratum ....... 46 
Table 8: 
Distribution of Protocol Deviations by Category, Type, and Study arm - All Enrolled 
Subjects ...................................................................................................................... 47 
Table 9: 
Solicited Adverse Event Grading Scale – Local ........................................................ 49 
Table 10: 
Solicited Adverse Event Grading Scale - Systemic ................................................... 50 
Table 11: 
Vital Signs Adverse Event Grading Scale .................................................................. 51 
Table 12: 
Laboratory Adverse Event Grading Scale .................................................................. 52 
Table 13: 
Ineligibility Summary of Screen Failures................................................................... 53 
Table 14: 
Analysis Populations by Study Arm, All Enrolled Subjects ...................................... 54 
Table 15: 
Subject Disposition by Study Arm - All Randomized Subjects ................................. 57 
Table 16: 
Dates of First Study Vaccination by Site and Study Arm - Safety Population .......... 58 
Table 17: 
Dates of Second Study Vaccination by Site, Study Arm, and Age Stratum - Safety 
Population ................................................................................................................... 58 
Table 18: 
Summary of Categorical Demographic and Baseline Characteristics by Site - All 
Enrolled Subjects ........................................................................................................ 59 
Table 19: 
Summary of Continuous Demographic and Baseline Characteristics by Site - All 
Enrolled Subjects ........................................................................................................ 60 
Table 20: 
Summary of Categorical Demographic and Baseline Characteristics by Study Arm - 
All Enrolled Subjects.................................................................................................. 61 
Table 21: 
Summary of Continuous Baseline Characteristics by Study Arm - All Enrolled 
Subjects ...................................................................................................................... 62 
Table 22: 
Summary of Subjects with Prior or Concurrent Medical Conditions by MedDRA 
System Organ Class and Study Arm - Safety Population .......................................... 63 
Table 23: 
Summaries of Hemagglutination Inhibition Antibody Against A/Hong 
Kong/125/2017 (H7N9) by Study Day and Study Arm - Modified Intent-to-Treat 
Population* ................................................................................................................. 64 
Table 24: 
Summaries of Hemagglutination Inhibition Antibody Against A/Hong 
Kong/125/2017 (H7N9) by Study Day and Study Arm - Per-Protocol Population* . 65 
Table 25: 
Summaries of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by 
Study Day and Study Arm - Modified Intent-to-Treat Population* ........................... 65 
Table 26: 
Summaries of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by 
Study Day and Study Arm - Per-Protocol Population* .............................................. 65 
Table 27: 
Summary of Hemagglutination Inhibition Antibody Against A/Hong Kong/125/2017 
(H7N9) by Study Arm and Age Categories at 21 Days Post Second Vaccination - 
Per-Protocol Population ............................................................................................. 66 
Table 28: 
Summary of Hemagglutination Inhibition Antibody Against A/Hong Kong/125/2017 
(H7N9) by Study Arm and Age Categories at 180 Days Post Second Vaccination - 
Per-Protocol Population ............................................................................................. 67 


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Table 29: 
Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by 
Study Arm and Age Categories at 21 Days Post Second Vaccination - Per-Protocol 
Population ................................................................................................................... 67 
Table 30: 
Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by 
Study Arm and Age Categories at 180 Days Post Second Vaccination - Per-Protocol 
Population ................................................................................................................... 67 
Table 31: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study 
Arm and Sex at 21 Days Post Second Vaccination - Per-Protocol Population .......... 68 
Table 32: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study 
Arm and Sex at 180 Days Post Second Vaccination - Per-Protocol Population ........ 68 
Table 33: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Study Arm and Sex at 
21 Days Post Second Vaccination - Per-Protocol Population .................................... 68 
Table 34: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Study Arm and Sex at 
180 Days Post Second Vaccination - Per-Protocol Population .................................. 68 
Table 35: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study 
Arm and BMI at 21 Days Post Second Vaccination - Per-Protocol Population ......... 69 
Table 36: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study 
Arm and BMI at 180 Days Post Second Vaccination - Per-Protocol Population ....... 69 
Table 37: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Study Arm and BMI at 
21 Days Post Second Vaccination - Per-Protocol Population .................................... 69 
Table 38: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Study Arm and BMI at 
180 Days Post Second Vaccination - Per-Protocol Population .................................. 69 
Table 39: 
Summary of Hemagglutination Inhibition Antibody Against A/Hong Kong/125/2017 
(H7N9) by Study Arm and Prior Seasonal Influenza Vaccination at 21 Days Post 
Second Vaccination - Per-Protocol Population .......................................................... 70 
Table 40: 
Summary of Hemagglutination Inhibition Antibody Against A/Hong Kong/125/2017 
(H7N9) by Study Arm, Age Stratum and Prior Seasonal Influenza Vaccination at 180 
Days Post Second Vaccination - Per-Protocol Population ......................................... 70 
Table 41: 
Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by 
Study Arm, Age Stratum and Prior Seasonal Influenza Vaccination at 21 Days Post 
Second Vaccination - Per-Protocol Population .......................................................... 70 
Table 42: 
Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by 
Study Arm, Age Stratum and Prior Seasonal Influenza Vaccination at 180 Days Post 
Second Vaccination - Per-Protocol Population .......................................................... 70 
Table 43: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
MF59 Adjuvant with HAI Seroconversion Against A/Hong Kong/125/2017 (H7N9) 
at 21 Days Post Second Study Vaccination - Per-Protocol Population ...................... 71 
Table 44: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
MF59 Adjuvant with Neut Seroconversion Against A/Hong Kong/125/2017 (H7N9) 
at 21 Days Post Second Study Vaccination - Per-Protocol Population ...................... 71 
Table 45: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
MF59 Adjuvant with HAI Seroconversion Against A/Hong Kong/125/2017 (H7N9) 
at 180 Days Post Second Study Vaccination - Per-Protocol Population .................... 71 
Table 46: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
MF59 Adjuvant with Neut Seroconversion Against A/Hong Kong/125/2017 (H7N9) 
at 180 Days Post Second Study Vaccination - Per-Protocol Population .................... 71 
Table 47: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
MF59 Adjuvant with HAI Seroconversion Against A/Hong Kong/125/2017 (H7N9) 
at 21 Days Post Second Study Vaccination, Adjusted for Baseline Covariates - Per-
Protocol Population .................................................................................................... 72 


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Table 48: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
MF59 Adjuvant with Neut Seroconversion Against A/Hong Kong/125/2017 (H7N9) 
at 21 Days Post Second Study Vaccination, Adjusted for Baseline Covariates - Per-
Protocol Population .................................................................................................... 73 
Table 49: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
MF59 Adjuvant with HAI Seroconversion Against A/Hong Kong/125/2017 (H7N9) 
at 180 Days Post Second Study Vaccination, Adjusted for Baseline Covariates - Per-
Protocol Population .................................................................................................... 73 
Table 50: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
MF59 Adjuvant with Neut Seroconversion Against A/Hong Kong/125/2017 (H7N9) 
at 180 Days Post Second Study Vaccination, Adjusted for Baseline Covariates - Per-
Protocol Population .................................................................................................... 73 
Table 51: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and MF59 Adjuvant with Log-Adjusted HAI Titer at 21 Days Post Second Study 
Vaccination - Per-Protocol Population ....................................................................... 74 
Table 52: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and MF59 Adjuvant with Log-Adjusted Neut Titer at 21 Days Post Second Study 
Vaccination - Per-Protocol Population ....................................................................... 74 
Table 53: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and MF59 Adjuvant with Log-Adjusted HAI Titer at 180 Days Post Second Study 
Vaccination - Per-Protocol Population ....................................................................... 74 
Table 54: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and MF59 Adjuvant with Log-Adjusted Neut Titer at 180 Days Post Second Study 
Vaccination - Per-Protocol Population ....................................................................... 74 
Table 55: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and MF59 Adjuvant with Log-Adjusted HAI Titer at 21 Days Post Second Study 
Vaccination, Adjusted for Baseline Covariates - Per-Protocol Population ................ 75 
Table 56: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and MF59 Adjuvant with Log-Adjusted Neut Titer at 21 Days Post Second Study 
Vaccination, Adjusted for Baseline Covariates, Per-Protocol Population ................. 76 
Table 57: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and MF59 Adjuvant with Log-Adjusted HAI Titer at 180 Days Post Second Study 
Vaccination, Adjusted for Baseline Covariates, Per-Protocol Population ................. 76 
Table 58: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and MF59 Adjuvant with Log-Adjusted Neut Titer at 180 Days Post Second Study 
Vaccination, Adjusted for Baseline Covariates, Per-Protocol Population ................. 76 
Table 59: 
Summaries of Hemagglutination Inhibition Antibody Against A/Shanghai/2/2013 
(H7N9) by Study Day and Study Arm, Per-Protocol Population* ............................. 77 
Table 60: 
Summaries of Hemagglutination Inhibition Antibody Against 
A/Guangdong/17SF003/2016 (H7N9) by Study Day and Study Arm, Per-Protocol 
Population* ................................................................................................................. 78 
Table 61: 
Summaries of Neutralizing Antibody Against A/Shanghai/2/2013 (H7N9) by Study 
Day and Study Arm, Per-Protocol Population* ......................................................... 78 
Table 62: 
Summaries of Neutralizing Antibody Against A/Guangdong/17SF003/2016 (H7N9) 
by Study Day and Study Arm, Per-Protocol Population* .......................................... 78 
Table 63: 
Overall Summary of Adverse Events – Safety Population* ...................................... 79 
Table 64: 
Number of Adverse Events Occurring in 5% of Subjects in Any Study Arm by 
MedDRA® System Organ Class and Preferred Term, and Treatment Group - Safety 
Population ................................................................................................................... 81 


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Table 65: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% 
Confidence Intervals by Symptom and Study Arm – Post Any Study Vaccination - 
Safety Population ....................................................................................................... 82 
Table 66: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% 
Confidence Intervals by Symptom and Study arm – Post Study Vaccination 1 – 
Safety Population ....................................................................................................... 83 
Table 67: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% 
Confidence Intervals by Symptom and Study arm– Post Study Vaccination 2 – Safety 
Population ................................................................................................................... 83 
Table 68: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
MF59 Adjuvant with Reporting Any Injection Site Event - Post Any Study 
Vaccination – Safety Population ................................................................................ 84 
Table 69: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
MF59 Adjuvant with Reporting Any Systemic Event - Post Any Study Vaccination – 
Safety Population ....................................................................................................... 84 
Table 70: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Maximum Severity and Study Arm– Post Any Study Vaccination – Safety Population
 .................................................................................................................................... 85 
Table 71: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Maximum Severity and Study arm– Post Study Vaccination 1 – Safety Population . 89 
Table 72: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Maximum Severity and Study arm – Post Study Vaccination 2 – Safety Population 89 
Table 73: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Severity, Day Post Study Vaccination, and Study arm – Post Any Study Vaccination 
– Safety Population .................................................................................................... 90 
Table 74: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Severity, Day Post Study Vaccination, and Study arm – Post Study Vaccination 1 – 
Safety Population ....................................................................................................... 93 
Table 75: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Severity, Day Post Study Vaccination, and Study arm – Post Study Vaccination 2 – 
Safety Population ....................................................................................................... 93 
Table 76: 
Number and Percentage of Subjects Experiencing Solicited Systemic Events for Dose 
1 Compared with Dose 2 by Study Arm – Safety Population .................................... 94 
Table 77: 
Number and Percentage of Subjects Experiencing Solicited Injection Site Events for 
Dose 1 Compared with Dose 2 by Study arm and Age Stratum – Safety Population 94 
Table 78: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events with 
95% Confidence Intervals by MedDRA® System Organ Class and Preferred Term, 
and Study Arm – Safety Population ........................................................................... 95 
Table 79: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events by 
MedDRA System Organ Class and Preferred Term, Maximum Severity, 
Relationship, and Study Arm – Safety Population ..................................................... 96 
Table 80: 
Number and Percentage of Subjects Experiencing Non-Serious Related Unsolicited 
Adverse Events by MedDRA System Organ Class and Preferred Term, Maximum 
Severity, and Study Arm – Safety Population ............................................................ 97 
Table 81: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events Within 
21 Days Post Study Vaccination by MedDRA System Organ Class and Preferred 
Term, Day Post Vaccination, and Study Arm – Safety Population ............................ 98 
Table 82: 
Number and Percentage of Subjects Experiencing Non-Serious, Related Unsolicited 
Adverse Events Within 21 Days Post Vaccination by MedDRA System Organ Class 
and Preferred Term, Study Vaccination, and Study Arm – Safety Population .......... 99 


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Table 83: 
Number of Unsolicited Adverse Events by MedDRA System Organ Class and 
Preferred Term, Day Post Vaccination, and Study Arm – Safety Population .......... 100 
Table 84: 
Listing of Serious Adverse Events – Safety Population ........................................... 101 
Table 85: 
Listing of Potentially Immune-Mediated Medical Conditions – Safety Population 102 
Table 86: 
Listing of New Onset Chronic Medical Conditions – Safety Population ................. 102 
Table 87: 
Listing of Non-Serious, Unsolicited, Moderate or Severe Adverse Events – Safety 
Population ................................................................................................................. 102 
Table 88: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Study Arm – 
All Laboratory Parameters – Safety Population ....................................................... 104 
Table 89: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Study arm – 
Hemoglobin – Safety Population ............................................................................. 105 
Table 90: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Study arm – 
Alanine aminotransferase (ALT) – Safety Population ............................................. 105 
Table 91: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Study arm – 
Total Bilirubin – Safety Population .......................................................................... 105 
Table 92: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Study arm – 
Creatinine – Safety Population ................................................................................. 105 
Table 93: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Study Arm – 
White Blood Cells – Safety Population .................................................................... 106 
Table 94: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Study Arm – 
Platelets – Safety Population .................................................................................... 106 
Table 95: 
Laboratory Summary Statistics of Value and Change from Baseline by Parameter, 
Study Day, and Study Arm – White Blood Cells - Safety Population ..................... 107 
Table 96: 
Laboratory Summary Statistics of Value and Change from Baseline by Parameter, 
Study Day, and Study Arm – Hemoglobin - Safety Population ............................... 107 
Table 97: 
Laboratory Summary Statistics of Value and Change from Baseline by Parameter, 
Study Day, and Study Arm – Platelets - Safety Population ..................................... 107 
Table 98: 
Laboratory Summary Statistics of Value and Change from Baseline by Parameter, 
Study Day, and Study Arm – Alanine aminotransferase (ALT) - Safety Population
 .................................................................................................................................. 107 
Table 99: 
Laboratory Summary Statistics of Value and Change from Baseline by Parameter, 
Study Day, and Study Arm –  Total Bilirubin - Safety Population .......................... 107 
Table 100: 
Laboratory Summary Statistics of Value and Change from Baseline by Parameter, 
Study Day, and Study Arm – Creatinine - Safety Population .................................. 107 
Table 101: 
Listing of Abnormal Laboratory Results - Chemistry .............................................. 109 
Table 102: 
Listing of Abnormal Laboratory Results - Hematology ........................................... 110 
Table 103: 
Vital Signs by Assessment, Maximum Severity, Study Day, and Study Arm – Any 
Assessment - Safety Population ............................................................................... 111 
Table 104: 
Vital Signs by Assessment, Maximum Severity, Study Day, and Study Arm – Oral 
Temperature - Safety Population .............................................................................. 111 
Table 105: 
Vital Signs by Assessment, Maximum Severity, Study Day, and Study Arm – 
Systolic Blood Pressure - Safety Population ............................................................ 112 
Table 106: 
Vital Signs by Assessment, Maximum Severity, Study Day, and Study Arm – 
Diastolic Blood Pressure - Analysis Population ....................................................... 112 
Table 107: 
Vital Signs by Assessment, Maximum Severity, Study Day, and Study Arm – Pulse - 
Safety Population ..................................................................................................... 112 
Table 108: 
Number and Percentage of Subjects with Prior and Concurrent Medications by WHO 
Drug Classification and Study Arm- Safety Population ........................................... 113 
 


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LIST OF TABLES 
Table 1: 
Study Design .............................................................................................................. 40 
Table 2: 
Schedule of Study Procedures – Vaccination Period ................................................. 41 
Table 3: 
Schedule of Study Procedures - Follow-Up Period (Including early termination and 
unscheduled visits) ..................................................................................................... 43 
Table 4: 
Power (%) to Detect Safety Events ............................................................................ 45 
Table 5: 
Precisions of Binomial Confidence Intervals ............................................................. 45 
Table 6: 
Minimum Detectable Difference in Proportion Responders with 80% Power .......... 45 
Table 7: 
Lower Confidence Bound for Difference in Proportion of Responders Between 
Adjuvanted (N = 100) and Unadjuvanted (N = 50) Arms, 18-64 Years Stratum ....... 46 
Table 8: 
Distribution of Protocol Deviations by Category, Type, and Study arm - All Enrolled 
Subjects ...................................................................................................................... 47 
Table 9: 
Solicited Adverse Event Grading Scale – Local ........................................................ 49 
Table 10: 
Solicited Adverse Event Grading Scale - Systemic ................................................... 50 
Table 11: 
Vital Signs Adverse Event Grading Scale .................................................................. 51 
Table 12: 
Laboratory Adverse Event Grading Scale .................................................................. 52 
Table 13: 
Ineligibility Summary of Screen Failures................................................................... 53 
Table 14: 
Analysis Populations by Study Arm, All Enrolled Subjects ...................................... 54 
Table 15: 
Subject Disposition by Study Arm - All Randomized Subjects ................................. 57 
Table 16: 
Dates of First Study Vaccination by Site and Study Arm - Safety Population .......... 58 
Table 17: 
Dates of Second Study Vaccination by Site, Study Arm, and Age Stratum - Safety 
Population ................................................................................................................... 58 
Table 18: 
Summary of Categorical Demographic and Baseline Characteristics by Site - All 
Enrolled Subjects ........................................................................................................ 59 
Table 19: 
Summary of Continuous Demographic and Baseline Characteristics by Site - All 
Enrolled Subjects ........................................................................................................ 60 
Table 20: 
Summary of Categorical Demographic and Baseline Characteristics by Study Arm - 
All Enrolled Subjects.................................................................................................. 61 
Table 21: 
Summary of Continuous Baseline Characteristics by Study Arm - All Enrolled 
Subjects ...................................................................................................................... 62 
Table 22: 
Summary of Subjects with Prior or Concurrent Medical Conditions by MedDRA 
System Organ Class and Study Arm - Safety Population .......................................... 63 
Table 23: 
Summaries of Hemagglutination Inhibition Antibody Against A/Hong 
Kong/125/2017 (H7N9) by Study Day and Study Arm - Modified Intent-to-Treat 
Population* ................................................................................................................. 64 
Table 24: 
Summaries of Hemagglutination Inhibition Antibody Against A/Hong 
Kong/125/2017 (H7N9) by Study Day and Study Arm - Per-Protocol Population* . 65 
Table 25: 
Summaries of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by 
Study Day and Study Arm - Modified Intent-to-Treat Population* ........................... 65 
Table 26: 
Summaries of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by 
Study Day and Study Arm - Per-Protocol Population* .............................................. 65 
Table 27: 
Summary of Hemagglutination Inhibition Antibody Against A/Hong Kong/125/2017 
(H7N9) by Study Arm and Age Categories at 21 Days Post Second Vaccination - 
Per-Protocol Population ............................................................................................. 66 
Table 28: 
Summary of Hemagglutination Inhibition Antibody Against A/Hong Kong/125/2017 
(H7N9) by Study Arm and Age Categories at 180 Days Post Second Vaccination - 
Per-Protocol Population ............................................................................................. 67 


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Table 29: 
Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by 
Study Arm and Age Categories at 21 Days Post Second Vaccination - Per-Protocol 
Population ................................................................................................................... 67 
Table 30: 
Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by 
Study Arm and Age Categories at 180 Days Post Second Vaccination - Per-Protocol 
Population ................................................................................................................... 67 
Table 31: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study 
Arm and Sex at 21 Days Post Second Vaccination - Per-Protocol Population .......... 68 
Table 32: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study 
Arm and Sex at 180 Days Post Second Vaccination - Per-Protocol Population ........ 68 
Table 33: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Study Arm and Sex at 
21 Days Post Second Vaccination - Per-Protocol Population .................................... 68 
Table 34: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Study Arm and Sex at 
180 Days Post Second Vaccination - Per-Protocol Population .................................. 68 
Table 35: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study 
Arm and BMI at 21 Days Post Second Vaccination - Per-Protocol Population ......... 69 
Table 36: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study 
Arm and BMI at 180 Days Post Second Vaccination - Per-Protocol Population ....... 69 
Table 37: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Study Arm and BMI at 
21 Days Post Second Vaccination - Per-Protocol Population .................................... 69 
Table 38: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Study Arm and BMI at 
180 Days Post Second Vaccination - Per-Protocol Population .................................. 69 
Table 39: 
Summary of Hemagglutination Inhibition Antibody Against A/Hong Kong/125/2017 
(H7N9) by Study Arm and Prior Seasonal Influenza Vaccination at 21 Days Post 
Second Vaccination - Per-Protocol Population .......................................................... 70 
Table 40: 
Summary of Hemagglutination Inhibition Antibody Against A/Hong Kong/125/2017 
(H7N9) by Study Arm, Age Stratum and Prior Seasonal Influenza Vaccination at 180 
Days Post Second Vaccination - Per-Protocol Population ......................................... 70 
Table 41: 
Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by 
Study Arm, Age Stratum and Prior Seasonal Influenza Vaccination at 21 Days Post 
Second Vaccination - Per-Protocol Population .......................................................... 70 
Table 42: 
Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by 
Study Arm, Age Stratum and Prior Seasonal Influenza Vaccination at 180 Days Post 
Second Vaccination - Per-Protocol Population .......................................................... 70 
Table 43: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
MF59 Adjuvant with HAI Seroconversion Against A/Hong Kong/125/2017 (H7N9) 
at 21 Days Post Second Study Vaccination - Per-Protocol Population ...................... 71 
Table 44: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
MF59 Adjuvant with Neut Seroconversion Against A/Hong Kong/125/2017 (H7N9) 
at 21 Days Post Second Study Vaccination - Per-Protocol Population ...................... 71 
Table 45: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
MF59 Adjuvant with HAI Seroconversion Against A/Hong Kong/125/2017 (H7N9) 
at 180 Days Post Second Study Vaccination - Per-Protocol Population .................... 71 
Table 46: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
MF59 Adjuvant with Neut Seroconversion Against A/Hong Kong/125/2017 (H7N9) 
at 180 Days Post Second Study Vaccination - Per-Protocol Population .................... 71 
Table 47: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
MF59 Adjuvant with HAI Seroconversion Against A/Hong Kong/125/2017 (H7N9) 
at 21 Days Post Second Study Vaccination, Adjusted for Baseline Covariates - Per-
Protocol Population .................................................................................................... 72 


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Table 48: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
MF59 Adjuvant with Neut Seroconversion Against A/Hong Kong/125/2017 (H7N9) 
at 21 Days Post Second Study Vaccination, Adjusted for Baseline Covariates - Per-
Protocol Population .................................................................................................... 73 
Table 49: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
MF59 Adjuvant with HAI Seroconversion Against A/Hong Kong/125/2017 (H7N9) 
at 180 Days Post Second Study Vaccination, Adjusted for Baseline Covariates - Per-
Protocol Population .................................................................................................... 73 
Table 50: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
MF59 Adjuvant with Neut Seroconversion Against A/Hong Kong/125/2017 (H7N9) 
at 180 Days Post Second Study Vaccination, Adjusted for Baseline Covariates - Per-
Protocol Population .................................................................................................... 73 
Table 51: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and MF59 Adjuvant with Log-Adjusted HAI Titer at 21 Days Post Second Study 
Vaccination - Per-Protocol Population ....................................................................... 74 
Table 52: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and MF59 Adjuvant with Log-Adjusted Neut Titer at 21 Days Post Second Study 
Vaccination - Per-Protocol Population ....................................................................... 74 
Table 53: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and MF59 Adjuvant with Log-Adjusted HAI Titer at 180 Days Post Second Study 
Vaccination - Per-Protocol Population ....................................................................... 74 
Table 54: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and MF59 Adjuvant with Log-Adjusted Neut Titer at 180 Days Post Second Study 
Vaccination - Per-Protocol Population ....................................................................... 74 
Table 55: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and MF59 Adjuvant with Log-Adjusted HAI Titer at 21 Days Post Second Study 
Vaccination, Adjusted for Baseline Covariates - Per-Protocol Population ................ 75 
Table 56: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and MF59 Adjuvant with Log-Adjusted Neut Titer at 21 Days Post Second Study 
Vaccination, Adjusted for Baseline Covariates, Per-Protocol Population ................. 76 
Table 57: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and MF59 Adjuvant with Log-Adjusted HAI Titer at 180 Days Post Second Study 
Vaccination, Adjusted for Baseline Covariates, Per-Protocol Population ................. 76 
Table 58: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose 
and MF59 Adjuvant with Log-Adjusted Neut Titer at 180 Days Post Second Study 
Vaccination, Adjusted for Baseline Covariates, Per-Protocol Population ................. 76 
Table 59: 
Summaries of Hemagglutination Inhibition Antibody Against A/Shanghai/2/2013 
(H7N9) by Study Day and Study Arm, Per-Protocol Population* ............................. 77 
Table 60: 
Summaries of Hemagglutination Inhibition Antibody Against 
A/Guangdong/17SF003/2016 (H7N9) by Study Day and Study Arm, Per-Protocol 
Population* ................................................................................................................. 78 
Table 61: 
Summaries of Neutralizing Antibody Against A/Shanghai/2/2013 (H7N9) by Study 
Day and Study Arm, Per-Protocol Population* ......................................................... 78 
Table 62: 
Summaries of Neutralizing Antibody Against A/Guangdong/17SF003/2016 (H7N9) 
by Study Day and Study Arm, Per-Protocol Population* .......................................... 78 
Table 63: 
Overall Summary of Adverse Events – Safety Population* ...................................... 79 
Table 64: 
Number of Adverse Events Occurring in 5% of Subjects in Any Study Arm by 
MedDRA® System Organ Class and Preferred Term, and Treatment Group - Safety 
Population ................................................................................................................... 81 


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Table 65: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% 
Confidence Intervals by Symptom and Study Arm – Post Any Study Vaccination - 
Safety Population ....................................................................................................... 82 
Table 66: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% 
Confidence Intervals by Symptom and Study arm – Post Study Vaccination 1 – 
Safety Population ....................................................................................................... 83 
Table 67: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% 
Confidence Intervals by Symptom and Study arm– Post Study Vaccination 2 – Safety 
Population ................................................................................................................... 83 
Table 68: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
MF59 Adjuvant with Reporting Any Injection Site Event - Post Any Study 
Vaccination – Safety Population ................................................................................ 84 
Table 69: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and 
MF59 Adjuvant with Reporting Any Systemic Event - Post Any Study Vaccination – 
Safety Population ....................................................................................................... 84 
Table 70: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Maximum Severity and Study Arm– Post Any Study Vaccination – Safety Population
 .................................................................................................................................... 85 
Table 71: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Maximum Severity and Study arm– Post Study Vaccination 1 – Safety Population . 89 
Table 72: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Maximum Severity and Study arm – Post Study Vaccination 2 – Safety Population 89 
Table 73: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Severity, Day Post Study Vaccination, and Study arm – Post Any Study Vaccination 
– Safety Population .................................................................................................... 90 
Table 74: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Severity, Day Post Study Vaccination, and Study arm – Post Study Vaccination 1 – 
Safety Population ....................................................................................................... 93 
Table 75: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, 
Severity, Day Post Study Vaccination, and Study arm – Post Study Vaccination 2 – 
Safety Population ....................................................................................................... 93 
Table 76: 
Number and Percentage of Subjects Experiencing Solicited Systemic Events for Dose 
1 Compared with Dose 2 by Study Arm – Safety Population .................................... 94 
Table 77: 
Number and Percentage of Subjects Experiencing Solicited Injection Site Events for 
Dose 1 Compared with Dose 2 by Study arm and Age Stratum – Safety Population 94 
Table 78: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events with 
95% Confidence Intervals by MedDRA® System Organ Class and Preferred Term, 
and Study Arm – Safety Population ........................................................................... 95 
Table 79: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events by 
MedDRA System Organ Class and Preferred Term, Maximum Severity, 
Relationship, and Study Arm – Safety Population ..................................................... 96 
Table 80: 
Number and Percentage of Subjects Experiencing Non-Serious Related Unsolicited 
Adverse Events by MedDRA System Organ Class and Preferred Term, Maximum 
Severity, and Study Arm – Safety Population ............................................................ 97 
Table 81: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events Within 
21 Days Post Study Vaccination by MedDRA System Organ Class and Preferred 
Term, Day Post Vaccination, and Study Arm – Safety Population ............................ 98 
Table 82: 
Number and Percentage of Subjects Experiencing Non-Serious, Related Unsolicited 
Adverse Events Within 21 Days Post Vaccination by MedDRA System Organ Class 
and Preferred Term, Study Vaccination, and Study Arm – Safety Population .......... 99 


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Table 83: 
Number of Unsolicited Adverse Events by MedDRA System Organ Class and 
Preferred Term, Day Post Vaccination, and Study Arm – Safety Population .......... 100 
Table 84: 
Listing of Serious Adverse Events – Safety Population ........................................... 101 
Table 85: 
Listing of Potentially Immune-Mediated Medical Conditions – Safety Population 102 
Table 86: 
Listing of New Onset Chronic Medical Conditions – Safety Population ................. 102 
Table 87: 
Listing of Non-Serious, Unsolicited, Moderate or Severe Adverse Events – Safety 
Population ................................................................................................................. 102 
Table 88: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Study Arm – 
All Laboratory Parameters – Safety Population ....................................................... 104 
Table 89: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Study arm – 
Hemoglobin – Safety Population ............................................................................. 105 
Table 90: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Study arm – 
Alanine aminotransferase (ALT) – Safety Population ............................................. 105 
Table 91: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Study arm – 
Total Bilirubin – Safety Population .......................................................................... 105 
Table 92: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Study arm – 
Creatinine – Safety Population ................................................................................. 105 
Table 93: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Study Arm – 
White Blood Cells – Safety Population .................................................................... 106 
Table 94: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Study Arm – 
Platelets – Safety Population .................................................................................... 106 
Table 95: 
Laboratory Summary Statistics of Value and Change from Baseline by Parameter, 
Study Day, and Study Arm – White Blood Cells - Safety Population ..................... 107 
Table 96: 
Laboratory Summary Statistics of Value and Change from Baseline by Parameter, 
Study Day, and Study Arm – Hemoglobin - Safety Population ............................... 107 
Table 97: 
Laboratory Summary Statistics of Value and Change from Baseline by Parameter, 
Study Day, and Study Arm – Platelets - Safety Population ..................................... 107 
Table 98: 
Laboratory Summary Statistics of Value and Change from Baseline by Parameter, 
Study Day, and Study Arm – Alanine aminotransferase (ALT) - Safety Population
 .................................................................................................................................. 107 
Table 99: 
Laboratory Summary Statistics of Value and Change from Baseline by Parameter, 
Study Day, and Study Arm –  Total Bilirubin - Safety Population .......................... 107 
Table 100: 
Laboratory Summary Statistics of Value and Change from Baseline by Parameter, 
Study Day, and Study Arm – Creatinine - Safety Population .................................. 107 
Table 101: 
Listing of Abnormal Laboratory Results - Chemistry .............................................. 109 
Table 102: 
Listing of Abnormal Laboratory Results - Hematology ........................................... 110 
Table 103: 
Vital Signs by Assessment, Maximum Severity, Study Day, and Study Arm – Any 
Assessment - Safety Population ............................................................................... 111 
Table 104: 
Vital Signs by Assessment, Maximum Severity, Study Day, and Study Arm – Oral 
Temperature - Safety Population .............................................................................. 111 
Table 105: 
Vital Signs by Assessment, Maximum Severity, Study Day, and Study Arm – 
Systolic Blood Pressure - Safety Population ............................................................ 112 
Table 106: 
Vital Signs by Assessment, Maximum Severity, Study Day, and Study Arm – 
Diastolic Blood Pressure - Analysis Population ....................................................... 112 
Table 107: 
Vital Signs by Assessment, Maximum Severity, Study Day, and Study Arm – Pulse - 
Safety Population ..................................................................................................... 112 
Table 108: 
Number and Percentage of Subjects with Prior and Concurrent Medications by WHO 
Drug Classification and Study Arm- Safety Population ........................................... 113 
 


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9.1  
Overall Study Design and Plan Description 
Table 1: 
Study Design 
Study Arms 
Day 1 
Day 22 
Study Arm 1, n=106 
Seqirus H7N9 vaccine 3.75 mcg 
plus MF59 adjuvant 
Seqirus H7N9 vaccine 3.75 mcg 
plus MF59 adjuvant 
Study Arm 2, n=106 
Seqirus H7N9 vaccine 7.5 mcg 
plus MF59 adjuvant 
Seqirus H7N9 vaccine 7.5 mcg plus 
MF59 adjuvant 
Study Arm 3, n=106 
Seqirus H7N9 vaccine 15 mcg 
plus MF59 adjuvant 
Seqirus H7N9 vaccine 15 mcg plus 
MF59 adjuvant 
Study Arm 4, n=53 
Seqirus H7N9 vaccine 15 mcg 
unadjuvanted 
Seqirus H7N9 vaccine 15 mcg 
unadjuvanted 
 
 


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


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


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


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


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9.7.1 Sample Size 
Table 4: 
Power (%) to Detect Safety Events  
Event 
Frequency 
N = 53 
N = 106 
N = 318 
≥10% 
Very Common 
>99 
>99 
>99 
≥1% 
Common 
41 
65 
95 
≥0.1% 
Uncommon 
5 
10 
27 
≥0.01% 
Rare 
<1 
1 
3 
 
Table 5: 
Precisions of Binomial Confidence Intervals 
N 
95% CI 
53 
36-64 
106 
40-60 
318 
44-56 
 
Table 6: 
Minimum Detectable Difference in Proportion Responders with 80% Power 
Assumed Proportion of subjects with titer ≥40 in 
comparator arm 
Minimum Detectable 
Difference (N = 100) 
0.40 
0.20 
0.50 
0.29 
0.60 
0.19 
0.70 
0.17 
0.80 
0.14 
0.90 
0.09 


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Table 7: 
Lower Confidence Bound for Difference in Proportion of Responders  
Between Adjuvanted (N = 100) and Unadjuvanted (N = 50) Arms, 18-64 Years 
Stratum 
Adjuvanted  
Study Arm 
Unadjuvanted 
Study Arm 
Difference 
Lower Confidence 
Bounda 
0.50 
0.10 
0.40 
0.26 
0.60 
0.10 
0.50 
0.36 
0.70 
0.10 
0.60 
0.46 
0.80 
0.10 
0.70 
0.56 
0.90 
0.10 
0.80 
0.67 
a Farrington-Manning confidence limits.  


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10.2 
Protocol Deviations 
Table 8: 
Distribution of Protocol Deviations by Category, Type, and Study arm - All 
Enrolled Subjects 
Category 
Deviation Type 
Study Arm 1 
3.75 mcg 
A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg 
A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg 
A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg 
A/H7N9  
(N=X) 
All Subjects 
(N=X) 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
Eligibility/enrollment 
Any type 
 
 
 
 
 
 
 
 
 
 
 
Did not meet 
inclusion criterion 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Met exclusion 
criterion 
 
 
 
 
 
 
 
 
 
 
 
ICF not signed 
prior to study 
procedures 
 
 
 
 
 
 
 
 
  
 
 
Other 
 
 
 
 
 
 
 
 
 
 
Treatment administration 
schedule 
Any type 
 
 
 
 
 
 
 
 
 
 
 
Out of window 
visit 
 
 
 
 
 
 
 
 
 
 
 
Missed visit/visit 
not conducted 
 
 
 
 
 
 
 
 
 
 
 
Missed treatment 
administration 
 
 
 
 
 
 
 
 
 
 
 
Delayed treatment 
administration 
 
 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
 
 
Follow-up visit schedule 
Any type 
 
 
 
 
 
 
 
 
 
 
 
Out of window 
visit 
 
 
 
 
 
 
 
 
 
 
 
Missed visit/visit 
not conducted 
 
 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
 
 
Protocol procedure/assessment 
Any type 
 
 
 
 
 
 
 
 
 
 
 
Incorrect version 
of ICF signed 
 
 
 
 
 
 
 
 
 
 
 
Blood not 
collected 
 
 
 
 
 
 
 
 
 
 
 
Too few aliquots 
obtained 
 
 
 
 
 
 
 
 
 
 
 
Specimen result 
not obtained 
 
 
 
 
 
 
 
 
 
 


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Table 8: 
Distribution of Protocol Deviations by Category, Type, and Study arm - All Enrolled 
Subjects (continued) 
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Category 
Deviation Type 
Study Arm 1 
3.75 mcg 
A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg 
A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg 
A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg 
A/H7N9  
(N=X) 
All Subjects 
(N=X) 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
# of 
Subj. 
# of 
Dev. 
 
Required 
procedure not 
conducted 
 
 
 
 
 
 
 
 
 
 
 
Required 
procedure done 
incorrectly 
 
 
 
 
 
 
 
 
 
 
 
Study product 
temperature 
excursion 
 
 
 
 
 
 
 
 
 
 
 
Specimen 
temperature 
excursion 
 
 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
 
 
Treatment administration 
Any type 
 
 
 
 
 
 
 
 
 
 
 
Required 
procedure done 
incorrectly 
 
 
 
 
 
 
 
 
 
 
 
Study product 
temperature 
excursion 
 
 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
 
 
Blinding policy/procedure 
Any type 
 
 
 
 
 
 
 
 
 
 
 
Treatment 
unblinded 
 
 
 
 
 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
 
 
Note: N = Number of subjects enrolled 


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12.2.2 Displays of Adverse Events 
Table 9: 
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 10: 
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 11: 
Vital Signs Adverse Event Grading Scale 
For all individuals, 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 12: 
Laboratory Adverse Event Grading Scale 
Hematology 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
WBC 103/µL (Decrease) 
2.5 – 3.9 
1.5 – 2.4 
<1.5 
WBC 103/µL (Increase) 
10.6 – 15.0 
15.1 – 20.0 
>20.0 
Hgb g/dL (Decrease) (Female) 
10.1 – 11.4 
8.5 – 10 
<8.5 
Hgb g/dL (Decrease) (Male) 
11.0 – 12.4 
9.5 – 10.9 
<9.5 
Platelets 103/µL (Decrease) 
125 – 139 
100 – 124 
<100 
Platelets 103/µL (Increase) 
416 – 550 
551– 750 
>750 
Chemistry 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
ALT IU/L (Increase) (Female) 
44 – 100 
101 – 200 
>200 
ALT IU/L (Increase) (Male) 
61 – 138 
139 – 275 
>275 
Total Bilirubin mg/dL (Increase) – 
when accompanied by any increase in 
ALT 
1.30 – 1.59 
1.60 – 1.80 
>1.80 
Total Bilirubin mg/dL (Increase) – 
when ALT is normal 
1.30 – 1.89 
1.90 – 2.40 
>2.40 
Creatinine mg/dL (Increase) 
(Female) 
1.1 – 1.7 
1.8 – 2.0 
>2.0 
Creatinine mg/dL (Increase) (Male) 
1.4 – 1.7 
1.8 – 2.0 
>2.0 
 
 


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14.1 
Description of Study Subjects 
14.1.1 Disposition of Subjects 
Table 13: 
Ineligibility Summary of Screen Failures 
Inclusion/Exclusion Category 
Inclusion/Exclusion Criterion 
na 
%b 
Inclusion and Exclusion 
Number of subjects failing any eligibility 
criterion 
x 
x 
Inclusion 
Any inclusion criterion 
x 
x 
 
[inclusion criterion 1] 
x 
x 
 
[inclusion criterion 2] 
x 
x 
 
[inclusion criterion 3] 
x 
x 
Exclusion 
Any exclusion criterion 
x 
x 
 
[exclusion criterion 1] 
x 
x 
 
[exclusion criterion 2] 
x 
x 
 
[exclusion criterion 3] 
x 
x 
a More than one criterion may be marked per subject. 
b Denominator for percentages is the total number of screen failures. 
 


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Table 14: 
Analysis Populations by Study Arm, All Enrolled Subjects 
Analysis Populations 
Reason Subjects Excluded 
Study Arm 1 
3.75 mcg 
A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg 
A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg 
A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg 
A/H7N9  
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Safety Population 
Any Reason 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Study Vaccination 1 Not Received 
 
 
 
 
 
 
 
 
 
 
Modified Intent to Treat 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 1 Not Received 
 
 
 
 
 
 
 
 
 
 
 
No Baseline Results Available 
 
 
 
 
 
 
 
 
 
 
 
No Post-Vaccination Results Available 
 
 
 
 
 
 
 
 
 
 
Per-Protocol, All Visits 
Found to be Ineligible After Baseline 
 
 
 
 
 
 
 
 
 
 
Per-Protocol, Day 8 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 1 Not Received 
 
 
 
 
 
 
 
 
 
 
 
No Baseline Results Available 
 
 
 
 
 
 
 
 
 
 
 
Ineligible at Baseline 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Non-Study Vaccination 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Immunosuppressive Medication 
 
 
 
 
 
 
 
 
 
 
 
No Day 9 Result Reported by Lab 
 
 
 
 
 
 
 
 
 
 
 
Lost to Follow-up Before Day 9 
 
 
 
 
 
 
 
 
 
 
 
Day 9 Visit Out of Window 
 
 
 
 
 
 
 
 
 
 
Per-Protocol, Day 22 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 1 Not Received 
 
 
 
 
 
 
 
 
 
 
 
No Baseline Results Available 
 
 
 
 
 
 
 
 
 
 
 
Ineligible at Baseline 
 
 
 
 
 
 
 
 
 
 


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Table 14: Analysis Populations by Study arm* (continued) 
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Analysis Populations 
Reason Subjects Excluded 
Study Arm 1 
3.75 mcg 
A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg 
A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg 
A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg 
A/H7N9  
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
 
Receipt of Non-Study Vaccination 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Immunosuppressive Medication 
 
 
 
 
 
 
 
 
 
 
 
No Day 22 Result Reported by Lab 
 
 
 
 
 
 
 
 
 
 
 
Lost to Follow-up Before Day 22 
 
 
 
 
 
 
 
 
 
 
 
Day 22 Visit Out of Window 
 
 
 
 
 
 
 
 
 
 
Per-Protocol, Day 29 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 1 Not Received 
 
 
 
 
 
 
 
 
 
 
 
No Baseline Results Available 
 
 
 
 
 
 
 
 
 
 
 
Ineligible at Baseline 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 2 Not Received 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 2 Out of Window 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Non-Study Vaccination 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Immunosuppressive Medication 
 
 
 
 
 
 
 
 
 
 
 
No Day 29 Result Reported by Lab 
 
 
 
 
 
 
 
 
 
 
 
Lost to Follow-up Before Day 29 
 
 
 
 
 
 
 
 
 
 
 
Day 29 Visit Out of Window 
 
 
 
 
 
 
 
 
 
 
Per-Protocol, Day 43 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 1 Not Received 
 
 
 
 
 
 
 
 
 
 
 
No Baseline Results Available 
 
 
 
 
 
 
 
 
 
 
 
Ineligible at Baseline 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 2 Not Received 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 2 Out of Window 
 
 
 
 
 
 
 
 
 
 


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Table 14: Analysis Populations by Study arm* (continued) 
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Analysis Populations 
Reason Subjects Excluded 
Study Arm 1 
3.75 mcg 
A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg 
A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg 
A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg 
A/H7N9  
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
 
Receipt of Non-Study Vaccination 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Immunosuppressive Medication 
 
 
 
 
 
 
 
 
 
 
 
No Day 43 Result Reported by Lab 
 
 
 
 
 
 
 
 
 
 
 
Lost to Follow-up Before Day 43 
 
 
 
 
 
 
 
 
 
 
 
Day 43 Visit Out of Window 
 
 
 
 
 
 
 
 
 
 
Per-Protocol, Day 202 
Any Reason 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 1 Not Received 
 
 
 
 
 
 
 
 
 
 
 
No Baseline Results Available 
 
 
 
 
 
 
 
 
 
 
 
Ineligible at Baseline 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 2 Not Received 
 
 
 
 
 
 
 
 
 
 
 
Study Vaccination 2 Out of Window 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Non-Study Vaccination 
 
 
 
 
 
 
 
 
 
 
 
Receipt of Immunosuppressive Medication 
 
 
 
 
 
 
 
 
 
 
 
No Day 202 Result Reported by Lab 
 
 
 
 
 
 
 
 
 
 
 
Lost to Follow-up Before Day 202 
 
 
 
 
 
 
 
 
 
 
 
Day 202 Visit Out of Window 
 
 
 
 
 
 
 
 
 
 
Note: N = Number of subjects randomized. 


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Table 15: 
Subject Disposition by Study Arm - All Randomized Subjects 
Subject 
Disposition 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Screened 
x 
-- 
x 
-- 
x 
-- 
x 
-- 
x 
-- 
Enrolled/Randomized 
x 
100 
x 
100 
x 
100 
x 
100 
x 
100 
Received Vaccination 1 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Received Vaccination 2 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Received All Scheduled Vaccinations a 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Completed Blood Draw for Primary Immunogenicity 
Analysis (Day 43) 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Included in Per-Protocol Primary Immunogenicity 
Analysis (Day 43)b 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Completed Primary Follow-up (Day 43)a 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Completed Final Study Visit (Day 387) 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
Note: N = Number of subjects randomized 
a Refer to Early Terminations or Discontinued Subjects Listing for reasons subjects discontinued from study vaccinations or terminated early. 
b Refer to Subjects Excluded from Analysis Populations Listing for reasons subjects are excluded from the Per-Protocol population. 


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Table 16: 
Dates of First Study Vaccination by Site and Study Arm - Safety Population 
Dates of Dosing 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(N=X) 
All Subjects 
(N=X) 
[Site 1] 
Total (Entire period of enrollment) 
x 
x 
x 
x 
x 
DDMMMYYYY-DDMMMYYYY 
 
 
 
 
 
…. 
 
 
 
 
 
[Site 2] 
Total (Entire period of enrollment) 
x 
x 
x 
x 
x 
DDMMMYYYY-DDMMMYYYY 
 
 
 
 
 
…. 
 
 
 
 
 
[Repeat for all sites] 
Note: N = Number of subjects in the Safety population.enrolled. 
 
Table with similar format: 
Table 17: 
Dates of Second Study Vaccination by Site, Study Arm, and Age Stratum - Safety Population 
 


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14.1.2 Demographic Data 
Table 18: 
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) 
[Site 5] 
(N=X) 
[Site 6] 
(N=X) 
[Site 7] 
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Sex  
Male 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Female 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BMI 
< 30 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
≥ 30 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ethnicity  
Not Hispanic or Latino 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
xx 
xx 
 
Hispanic or Latino 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Not Reported 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Race  
American Indian or Alaska Native 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
xx 
xx 
 
Asian 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Native Hawaiian or Other Pacific 
Islander 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Black or African American 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
White 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Multi-Racial 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior Seasonal Influenza 
Vaccination 
2016-2017 only 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2017-2018 only 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2018-2019 only 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N = Number of subjects enrolled 


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Table 19: 
Summary of Continuous Demographic and Baseline Characteristics by Site - All Enrolled Subjects 
Variable 
Statistic 
[Site 1] 
(N=X) 
[Site 2] 
(N=X) 
[Site 3] 
(N=X) 
[Site 4] 
(N=X) 
[Site 5] 
(N=X) 
[Site 6] 
(N=X) 
[Site 7] 
(N=X) 
All 
Subjects 
(N=X) 
Age 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Standard Deviation 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
x 
x 
x 
x 
x 
 
Maximum 
x 
x 
x 
x 
x 
x 
x 
x 
BMI 
Mean 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Standard Deviation 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
x 
x 
x 
x 
x 
 
Maximum 
x 
x 
x 
x 
x 
x 
x 
x 
Note: N = Number of subjects enrolled 
 


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Table 20: 
Summary of Categorical Demographic and Baseline Characteristics by Study Arm - All Enrolled Subjects 
Variable 
Characteristic 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(N=X) 
All 
Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Sex  
Male 
 
 
 
 
 
 
 
 
 
 
 
Female 
 
 
 
 
 
 
 
 
 
 
BMI 
< 30 
 
 
 
 
 
 
 
 
 
 
 
≥ 30 
 
 
 
 
 
 
 
 
 
 
Ethnicity  
Not Hispanic or Latino 
 
 
 
 
 
 
 
 
 
 
 
Hispanic or Latino 
 
 
 
 
 
 
 
 
 
 
 
Not Reported 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
Race  
American Indian or Alaska Native 
 
 
 
 
 
 
 
 
 
 
 
Asian 
 
 
 
 
 
 
 
 
 
 
 
Native Hawaiian or Other Pacific Islander 
 
 
 
 
 
 
 
 
 
 
 
Black or African American 
 
 
 
 
 
 
 
 
 
 
 
White 
 
 
 
 
 
 
 
 
 
 
 
Multi-Racial 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
Prior Seasonal Influenza 
Vaccination 
2016-2017 only 
 
 
 
 
 
 
 
 
 
 
 
2017-2018 only 
 
 
 
 
 
 
 
 
 
 
 
2018-2019 only 
 
 
 
 
 
 
 
 
 
 
 
Neither 
 
 
 
 
 
 
 
 
 
 
 
Unknown 
 
 
 
 
 
 
 
 
 
 
Note: N = Number of subjects enrolled 


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Table 21: 
Summary of Continuous Baseline Characteristics by Study Arm - All Enrolled Subjects 
Variable 
Statistic 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(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 
 
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 
 
Minimum 
x 
x 
x 
x 
x 
 
Maximum 
x 
x 
x 
x 
x 
Note: N = Number of subjects enrolled. 
 
 
 


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14.1.3 Summary of Prior or Concurrent Medical Conditions 
Table 22: 
Summary of Subjects with Prior or Concurrent Medical Conditions by MedDRA System Organ Class and Study Arm - 
Safety Population 
MedDRA System Organ Class 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(N=X) 
All Subjects 
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Any SOC 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
[SOC 1] 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
[SOC 2] 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
… 
 
 
 
 
 
 
 
 
 
 
Note: N=Number of subjects in the Safety population; n = Number of subjects reporting medical history within the specified SOC. A subject is only counted once per SOC. 


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14.2 
Immunogenicity Tables 
14.2.1 Immune Response Against 2017 A/H7N9 
Table 23: 
Summaries of Hemagglutination Inhibition Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Day and Study Arm - 
Modified Intent-to-Treat Population* 
Time Point 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(N=X) 
Day 1 (Pre-Vaccination 1) 
 
 
 
 
n 
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) 
Titer ≥ 1:40 - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
7 Days Post Vaccination 1 
 
 
 
 
n 
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) 
Seroconversion - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Titer ≥ 1:40 - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
21 Days Post Vaccination 1 
 
 
 
 
n 
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) 
Seroconversion - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Titer ≥ 1:40 - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
7 Days Post Vaccination 2 
 
 
 
 
n 
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) 
Seroconversion - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Titer ≥ 1:40 - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 


Statistical Analysis Plan - DMID Protocol: 17-0076  
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Table 23: Summaries of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study Day and Study arm, Modified Intent-to-
Treat Population (continued) 
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Time Point 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(N=X) 
21 Days Post Vaccination 2 
 
 
 
 
n 
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) 
Seroconversion - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Titer ≥ 1:40 - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
180 Days Post Vaccination 2 
 
 
 
 
n 
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) 
Seroconversion - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Titer ≥ 1:40 - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Note: N=number of subjects in the Modified Intent-to-Treat population.; n = Number of subjects with available results. 
GMT = Geometric Mean Titer; CI = Confidence Interval. 
a95% CIs calculated using Clopper-Pearson exact methods. 
Tables with similar format: 
Table 24: 
Summaries of Hemagglutination Inhibition Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Day and Study Arm - 
Per-Protocol Population* 
Table 25: 
Summaries of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Day and Study Arm - Modified Intent-
to-Treat Population* 
Table 26: 
Summaries of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Day and Study Arm - Per-Protocol 
Population* 
 


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Table 27: 
Summary of Hemagglutination Inhibition Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Arm and Age 
Categories at 21 Days Post Second Vaccination - Per-Protocol Population 
 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(N=X) 
Age 19-34 years 
 
 
 
 
 n  
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) 
 Seroconversion - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
 Titer ≥ 1:40 - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Age 35-49 years 
 
 
 
 
 n  
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) 
 Seroconversion - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
 Titer ≥ 1:40 - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Age 50-64 years 
 
 
 
 
 n  
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) 
 Seroconversion - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
 Titer ≥ 1:40 - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Note: N=number of subjects in the Modified Intent-to-Treat population.; n = Number of subjects with available results. 
GMT = Geometric Mean Titer; CI = Confidence Interval. 
a95% CIs calculated using Clopper-Pearson exact methods. 
 
 
 


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Tables with similar format: 
Table 28: 
Summary of Hemagglutination Inhibition Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Arm and Age 
Categories at 180 Days Post Second Vaccination - Per-Protocol Population 
Table 29: 
Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Arm and Age Categories at 21 Days 
Post Second Vaccination - Per-Protocol Population 
Table 30: 
Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Arm and Age Categories at 180 Days 
Post Second Vaccination - Per-Protocol Population 
 
 


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Table 31: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study Arm and Sex at 21 Days Post Second 
Vaccination - Per-Protocol Population 
 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(N=X) 
Female 
 
 
 
 
 n  
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) 
Seroconversion - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Titer ≥ 1:40 - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Male 
 
 
 
 
 n  
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) 
Seroconversion - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
 Titer ≥ 1:40 - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Note: N = Number of subjects in the Per-Protocol population; n = Number of subjects with available results. 
GMT = Geometric Mean Titer; CI = Confidence Interval. 
a 95% CIs calculated using Clopper-Pearson exact methods. 
Tables with similar format: 
Table 32: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study Arm and Sex at 180 Days Post Second 
Vaccination - Per-Protocol Population 
Table 33: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Study Arm and Sex at 21 Days Post Second Vaccination - Per-
Protocol Population 
Table 34: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Study Arm and Sex at 180 Days Post Second Vaccination - Per-
Protocol Population 


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Table 35: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study Arm and BMI at 21 Days Post Second 
Vaccination - Per-Protocol Population 
 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(N=X) 
BMI < 30 
 
 
 
 
 n  
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) 
 Seroconversion - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
 Titer ≥ 1:40 - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
BMI ≥ 30 
 
 
 
 
 n  
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) 
 Seroconversion - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
 Titer ≥ 1:40 - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Note: N = Number of subjects in the Per-Protocol population; n = Number of subjects with available results. 
GMT = Geometric Mean Titer; CI = Confidence Interval. 
a 95% CIs calculated using Clopper-Pearson exact methods. 
Tables with similar format: 
Table 36: 
Summary of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 by Study Arm and BMI at 180 Days Post Second 
Vaccination - Per-Protocol Population 
Table 37: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Study Arm and BMI at 21 Days Post Second Vaccination - Per-
Protocol Population 
Table 38: 
Summary of Neutralizing Antibody Against 2017 A/H7N9 by Study Arm and BMI at 180 Days Post Second Vaccination - Per-
Protocol Population 
 
 


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Table 39: 
Summary of Hemagglutination Inhibition Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Arm and Prior 
Seasonal Influenza Vaccination at 21 Days Post Second Vaccination - Per-Protocol Population 
 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(N=X) 
Did Not Receive 2017-2018 or 
2018-2019 Seasonal Influenza 
Vaccination 
 
 
 
 
 n  
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) 
 Seroconversion - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
 Titer ≥ 1:40 - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Received 2017-2018 or 2018-
2019 Seasonal Influenza 
Vaccination 
 
 
 
 
 n  
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) 
 Seroconversion - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
 Titer ≥ 1:40 - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Note: N = Number of subjects in the Per-Protocol population; n = Number of subjects with available results. 
GMT = Geometric Mean Titer; CI = Confidence Interval. 
a 95% CIs calculated using Clopper-Pearson exact methods. 
Tables with similar format: 
Table 40: 
Summary of Hemagglutination Inhibition Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Arm, Age Stratum and 
Prior Seasonal Influenza Vaccination at 180 Days Post Second Vaccination - Per-Protocol Population 
Table 41: 
Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Arm, Age Stratum and Prior Seasonal 
Influenza Vaccination at 21 Days Post Second Vaccination - Per-Protocol Population 
Table 42: 
Summary of Neutralizing Antibody Against A/Hong Kong/125/2017 (H7N9) by Study Arm, Age Stratum and Prior Seasonal 
Influenza Vaccination at 180 Days Post Second Vaccination - Per-Protocol Population


Statistical Analysis Plan - DMID Protocol: 17-0076  
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Table 43: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and MF59 Adjuvant with HAI Seroconversion 
Against A/Hong Kong/125/2017 (H7N9) at 21 Days Post Second Study Vaccination - Per-Protocol Population 
Model Parameter 
Parameter Estimate 
SE 
p-value 
Odds Ratio 
95%CI 
Intercept 
xxx.x 
xxx.x 
x.xxx 
- 
- 
Study Arm 
 
 
 
 
 
 15 mcg without MF59 adjuvant (reference) 
- 
- 
- 
- 
- 
 3.75 mcg with MF59 adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 7.5 mcg with MF59 adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 15 mcg MF59 adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Note: N = Number of subjects with results available at 21 days post second vaccination in the Per-Protocol population. XX subjects missing covariate data were excluded from 
this analysis.  
 
Tables with similar format: 
 
Table 44: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and MF59 Adjuvant with Neut Seroconversion 
Against A/Hong Kong/125/2017 (H7N9) at 21 Days Post Second Study Vaccination - Per-Protocol Population 
Table 45: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and MF59 Adjuvant with HAI Seroconversion 
Against A/Hong Kong/125/2017 (H7N9) at 180 Days Post Second Study Vaccination - Per-Protocol Population 
Table 46: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and MF59 Adjuvant with Neut Seroconversion 
Against A/Hong Kong/125/2017 (H7N9) at 180 Days Post Second Study Vaccination - Per-Protocol Population 
 


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Table 47: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and MF59 Adjuvant with HAI Seroconversion 
Against A/Hong Kong/125/2017 (H7N9) at 21 Days Post Second Study Vaccination, Adjusted for Baseline Covariates - Per-
Protocol Population  
Model Parameter 
Parameter Estimate 
SE 
p-value 
Odds Ratio 
95%CI 
Intercept 
xxx.x 
xxx.x 
x.xxx 
- 
- 
Study Arm 
 
 
 
 
 
15 mcg without MF59 Adjuvant (reference) 
- 
- 
- 
- 
- 
 3.75 mcg with MF59 Adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 7.5 mcg with MF59 Adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 15 mcg with MF59 Adjuvant 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Age 
 
 
 
 
 
 19-34 (reference) 
- 
- 
- 
- 
- 
 35-49  
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 50-64  
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 2017-2018 or 2018-2019 
Seasonal Influenza Vaccine (reference) 
- 
- 
- 
- 
- 
 Received 2017-2018 or 2018-2019 Seasonal 
Influenza Vaccine 
xxx.x 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
Note: N = Number of subjects with results available at 21 days post second vaccination in the Per-Protocol population. XX subjects missing covariate data were excluded from 
this analysis. 
 
 
 


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Tables with similar format: 
Table 48: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and MF59 Adjuvant with Neut Seroconversion 
Against A/Hong Kong/125/2017 (H7N9) at 21 Days Post Second Study Vaccination, Adjusted for Baseline Covariates - Per-
Protocol Population  
Table 49: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and MF59 Adjuvant with HAI Seroconversion 
Against A/Hong Kong/125/2017 (H7N9) at 180 Days Post Second Study Vaccination, Adjusted for Baseline Covariates - Per-
Protocol Population  
Table 50: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and MF59 Adjuvant with Neut Seroconversion 
Against A/Hong Kong/125/2017 (H7N9) at 180 Days Post Second Study Vaccination, Adjusted for Baseline Covariates - Per-
Protocol Population  
 
 


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Table 51: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose and MF59 Adjuvant with Log-Adjusted 
HAI Titer at 21 Days Post Second Study Vaccination - Per-Protocol Population 
Model Parameter 
Parameter Estimate 
SE 
95%CI 
p-value 
Intercept 
xxx.x 
xxx.x 
- 
x.xxx 
Study Arm 
 
 
 
 
15 mcg without MF59 adjuvant (reference) 
- 
- 
- 
- 
3.75 mcg with MF59 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
7.5 mcg with MF59 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 15 mcg with MF59 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Note: N = Number of subjects with results available at 21 days post second vaccination in the Per-Protocol population. XX subjects missing covariate data were excluded from 
this analysis 
Tables with similar format: 
Table 52: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose and MF59 Adjuvant with Log-Adjusted 
Neut Titer at 21 Days Post Second Study Vaccination - Per-Protocol Population  
Table 53: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose and MF59 Adjuvant with Log-Adjusted 
HAI Titer at 180 Days Post Second Study Vaccination - Per-Protocol Population  
Table 54: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose and MF59 Adjuvant with Log-Adjusted 
Neut Titer at 180 Days Post Second Study Vaccination - Per-Protocol Population  
 


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Table 55: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose and MF59 Adjuvant with Log-Adjusted 
HAI Titer at 21 Days Post Second Study Vaccination, Adjusted for Baseline Covariates - Per-Protocol Population  
Model Parameter 
Parameter Estimate 
SE 
95%CI 
p-value 
Intercept 
xxx.x 
xxx.x 
- 
x.xxx 
Study Arm 
 
 
 
 
 15 mcg without MF59 adjuvant (reference) 
- 
- 
- 
- 
 3.75 mcg with MF59 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 7.5 mcg with MF59 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 15 mcg with MF59 adjuvant 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Age 
 
 
 
 
 19-34 (reference) 
- 
- 
- 
- 
 35-49 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
 50-64 
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 2017-2018 or 2018-2019 Seasonal 
Influenza Vaccine (reference) 
- 
- 
- 
- 
Received 2017-2018 or 2018-2019 Seasonal Influenza 
Vaccine 
xxx.x 
xxx.x 
xx.x-xx.x 
x.xxx 
Note: N = Number of subjects with results available at 21 days post second vaccination in the Per-Protocol population. XX subjects missing covariate data were excluded from 
this analysis  
 
 
 


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Tables with similar format: 
 
Table 56: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose and MF59 Adjuvant with Log-Adjusted 
Neut Titer at 21 Days Post Second Study Vaccination, Adjusted for Baseline Covariates, Per-Protocol Population 
Table 57: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose and MF59 Adjuvant with Log-Adjusted 
HAI Titer at 180 Days Post Second Study Vaccination, Adjusted for Baseline Covariates, Per-Protocol Population 
Table 58: 
Multiple Linear Regression Model to Evaluate the Relationship of HA Antigen Dose and MF59 Adjuvant with Log-Adjusted 
Neut Titer at 180 Days Post Second Study Vaccination, Adjusted for Baseline Covariates, Per-Protocol Population


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Table 59: 
Summaries of Hemagglutination Inhibition Antibody Against A/Shanghai/2/2013 (H7N9) by Study Day and Study Arm, Per-
Protocol Population* 
Time Point 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(N=X) 
Day 1 (Pre Vaccination 1) 
 
 
 
 
n 
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) 
Titer ≥ 1:40 - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Day 21 Post Vaccination 2 
 
 
 
 
n 
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) 
Seroconversion - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Titer ≥ 1:40 - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Day 180 Post Vaccination 2 
 
 
 
 
n 
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) 
Seroconversion - % (95% CIa) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
xx (xx, xx) 
Titer ≥ 1:40 - % (95% CIa) 
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 available results;  
GMT = Geometric Mean Titer; CI = Confidence Interval 
a95% CIs calculated using Clopper-Pearson exact methods. 
 
 
 


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Tables with similar format: 
Table 60: 
Summaries of Hemagglutination Inhibition Antibody Against A/Guangdong/17SF003/2016 (H7N9) by Study Day and Study 
Arm, Per-Protocol Population* 
Table 61: 
Summaries of Neutralizing Antibody Against A/Shanghai/2/2013 (H7N9) by Study Day and Study Arm, Per-Protocol 
Population* 
Table 62: 
Summaries of Neutralizing Antibody Against A/Guangdong/17SF003/2016 (H7N9) by Study Day and Study Arm, Per-
Protocol Population*


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14.3 
Safety Data 
14.3.1 Displays of Adverse Events 
Table 63: 
Overall Summary of Adverse Events – Safety Population* 
 
Study Arm 1 
3.75 mcg 
A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg 
A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg 
A/H7N9  
+ MF59 
(N=X) 
Study Arm 
4 
15 mcg 
A/H7N9  
(N=X) 
All Subjects  
(N=X) 
Subjectsa with 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
 
 
 
 
 
 
 
 
 
 
 
At least one injection site solicited adverse event 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
At least one systemic solicited adverse event 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
At least one unsolicited adverse event 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
At least one related unsolicited adverse event 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
     Mild (Grade 1) 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
     Moderate (Grade 2)  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
     Severe (Grade 3)  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
At least one severe (Grade 3) unsolicited adverse event 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
     Related  
x 
x 
x 
x 
x 
x 
x 
x 
X 
x 
     Unrelated 
x 
x 
x 
x 
x 
x 
x 
x 
X 
x 
At least one serious adverse eventb 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
At least one related, serious adverse event 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
At least one adverse event leading to early terminationc  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
At least one medically attended adverse event 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 


Statistical Analysis Plan - DMID Protocol: 17-0076  
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Table 63: Overall Summary of Adverse Events (continued) 
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Study Arm 1 
3.75 mcg 
A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg 
A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg 
A/H7N9  
+ MF59 
(N=X) 
Study Arm 
4 
15 mcg 
A/H7N9  
(N=X) 
All Subjects  
(N=X) 
Subjectsa with 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
At least one new onset chronic medical condition 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
At least one potentially immune mediated medical condition 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Note: 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 Section 14.3.2. 
c As reported on the Adverse Event eCRF. 
 


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Table 64: 
Number of Adverse Events Occurring in 5% of Subjects in Any Study Arm by MedDRA® System Organ Class and Preferred 
Term, and Treatment Group - Safety Population 
[Implementation note: This table includes solicited events, unsolicited events, and clinical laboratory events. Sort by SOC then PT] 
Preferred Term 
MedDRA System 
Organ Class 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(N=X) 
All Subjects  
(N=X) 
 
 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
n 
% 
Events 
Serious Adverse Events 
All  
All 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
PT1 
SOC1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Etc. 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other (Non-serious) Adverse Events 
All  
All 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
PT1 
SOC1 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Etc 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N = number of subjects in the Safety population (number of subjects at risk); n= number of subjects reporting event; Events = total frequency of events reported.  
MedDRA Version X.X. 
 


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14.3.1.1 
Solicited Adverse Events 
Table 65: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom and 
Study Arm – Post Any Study Vaccination - Safety Population 
Symptom 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(N=X) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
Any Symptom 
x 
xx  
(xx-xx) 
x 
xx  
(xx-xx) 
x 
xx  
(xx-xx) 
x 
xx  
(xx-xx) 
Any Systemic Symptom 
 
 
 
 
 
 
 
 
Fever 
 
 
 
 
 
 
 
 
Feverishness 
 
 
 
 
 
 
 
 
Fatigue 
 
 
 
 
 
 
 
 
Malaise 
 
 
 
 
 
 
 
 
Myalgia 
 
 
 
 
 
 
 
 
Arthralgia 
 
 
 
 
 
 
 
 
Headache 
 
 
 
 
 
 
 
 
Nausea 
 
 
 
 
 
 
 
 
Any Injection Site Symptom 
 
 
 
 
 
 
 
 
Pain 
 
 
 
 
 
 
 
 
Tenderness 
 
 
 
 
 
 
 
 
Pruritus 
 
 
 
 
 
 
 
 
Ecchymosis 
 
 
 
 
 
 
 
 
Ecchymosis (measurement) 
 
 
 
 
 
 
 
 
Erythema 
 
 
 
 
 
 
 
 
Erythema (measurement) 
 
 
 
 
 
 
 
 
Induration/Swelling 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0076  
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Table 65: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom and Study 
Arm – Post Any Study Vaccination - Safety Population (continued) 
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Symptom 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(N=X) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
Induration/Swelling (measurement) 
 
 
 
 
 
 
 
 
Note: N = Number of subjects in the Safety population. 
95% CI estimated using Clopper-Pearson exact method 
Tables with similar format: 
Table 66: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom and Study 
arm – Post Study Vaccination 1 – Safety Population 
[Footnote update] N = Number of subjects in the Safety population who received the first vaccination. 
 
Table 67: 
Number and Percentage of Subjects Experiencing Solicited Events with 95% Confidence Intervals by Symptom and Study 
arm– Post Study Vaccination 2 – Safety Population 
[Footnote update] N = Number of subjects in the Safety population who received the second vaccination. 
 


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Table 68: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and MF59 Adjuvant with Reporting Any 
Injection Site Event - Post Any Study Vaccination – Safety Population 
Model Parameter 
Parameter 
Estimate 
 
SE 
p-value 
Odds Ratio 
95%CI 
Intercept 
xxx.x 
 
xxx.x 
x.xxx 
- 
- 
Study Arm 
 
 
 
 
 
 
 15 mcg with MF59 adjuvant (reference) 
- 
 
- 
- 
- 
- 
 3.75 mcg with MF59 adjuvant 
xxx.x 
 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 7.5 mcg with MF59 adjuvant 
xxx.x 
 
xxx.x 
x.xxx 
xx.x 
xx.x-xx.x 
 15 mcg without MF59 adjuvant 
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 69: 
Logistic Regression Model to Evaluate the Relationship of HA Antigen Dose and MF59 Adjuvant with Reporting Any 
Systemic Event - Post Any Study Vaccination – Safety Population


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Table 70: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity and 
Study Arm– Post Any Study Vaccination – Safety Population 
Symptom 
Severity 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(N=X) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
Any Symptom 
None 
x 
xx (xx-xx) 
x 
xx (xx-xx) 
x 
xx (xx-xx) 
x 
xx (xx-xx) 
 
Mild 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
Any Systemic Symptom 
None 
x 
xx (xx-xx) 
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 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0076  
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Table 70: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity and Study arm – Post 
Any Study Vaccination – Safety Population (continued) 
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Symptom 
Severity 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(N=X) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
 
Mild 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
Myalgia 
None 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
Arthralgia 
None 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
Headache 
None 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
Nausea 
None 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
Any Injection Site 
Symptom 
None 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0076  
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Table 70: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity and Study arm – Post 
Any Study Vaccination – Safety Population (continued) 
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Symptom 
Severity 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(N=X) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
 
Mild 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
Pain 
None 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
Tenderness 
None 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
Pruritus 
None 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
Ecchymosis 
None 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
Ecchymosis 
(measurement) 
None 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0076  
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Table 70: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity and Study arm – Post 
Any Study Vaccination – Safety Population (continued) 
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Symptom 
Severity 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(N=X) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
 
Mild 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
Erythema 
None 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
Erythema (measurement) 
None 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
Induration/Swelling 
None 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
Induration/Swelling 
(measurement) 
None 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 


Statistical Analysis Plan - DMID Protocol: 17-0076  
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Table 70: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity and Study arm – Post 
Any Study Vaccination – Safety Population (continued) 
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Symptom 
Severity 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(N=X) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
n 
%  
(95% CI) 
Note: N = Number of subjects in the Safety population. 
95% CI estimated using Clopper-Pearson exact method. 
Severity is the maximum severity reported over all solicited symptoms post dosing for each subject.   
 
Tables with similar format: 
Table 71: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity and Study arm– Post 
Study Vaccination 1 – Safety Population 
[Footnote Update] N = Number of subjects in the Safety population who received the first study vaccination. 
 
Table 72: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Maximum Severity and Study arm – Post 
Study Vaccination 2 – Safety Population 
[Footnote Update] N = Number of subjects in the Safety population who received the second study vaccination. 
 
.


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Table 73: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Severity, Day Post Study Vaccination, and 
Study arm – Post Any Study Vaccination – Safety Population 
Symptom 
Severity 
Pre-
Vac. 
Post-
Vac. 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Day 8+ 
 
 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Study Arm 1: 3.75 mcg A/H7N9 + MF59 (N=X) 
All Subjects 
Any Symptom 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Any Systemic Symptom 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fever 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Feverishness 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fatigue 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table 73: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Severity, Day Post Study Vaccination, and 
Study arm – Post Any Study Vaccination (continued) 
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Symptom 
Severity 
Pre-
Vac. 
Post-
Vac. 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Day 8+ 
 
 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Malaise 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Myalgia 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Arthralgia 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Headache 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nausea 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Any Injection Site Symptom 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table 73: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Severity, Day Post Study Vaccination, and 
Study arm – Post Any Study Vaccination (continued) 
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Symptom 
Severity 
Pre-
Vac. 
Post-
Vac. 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Day 8+ 
 
 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table 73: Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Severity, Day Post Study Vaccination, and 
Study arm – Post Any Study Vaccination (continued) 
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Symptom 
Severity 
Pre-
Vac. 
Post-
Vac. 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Day 8+ 
 
 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Erythema (measurement) 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Induration/Swelling 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Induration/Swelling (measurement) 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mild 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[repeat for all study arms] 
Note: N = Number of subjects in the Safety population. Severity is the maximum severity reported post dosing for each subject for each day. 
Tables with similar format: 
Table 74: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Severity, Day Post Study Vaccination, and 
Study arm – Post Study Vaccination 1 – Safety Population 
Table 75: 
Number and Percentage of Subjects Experiencing Solicited Events by Symptom, Severity, Day Post Study Vaccination, and 
Study arm – Post Study Vaccination 2 – Safety Population 
 


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Table 76: 
Number and Percentage of Subjects Experiencing Solicited Systemic Events for Dose 1 Compared with Dose 2 
by Study Arm – Safety Population 
 
 
Study Vaccination 2 
Study Arm 
Study Vaccination 1 
Subjects with No 
Symptoms 
Subjects with Mild or Greater 
Symptoms 
Total Number of Subjects 
n (Percent) 
[p-value*] 
Study Arm 1  
3.75 mcg A/H7N9 
+ MF59 
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 Arm 2  
7.5 mcg A/H7N9 + 
MF59 
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 Arm 3  
15 mcg A/H7N9 + 
MF59 
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 Arm 4 
15 mcg A/H7N9  
Subjects with No Symptoms  
x (%) 
x (%) 
x (%) 
Subjects with Mild or Greater 
Symptoms  
x (%) 
x (%) 
x (%) 
Total Number of Subjects  
x (%) 
x (%) 
x (100%) 
[0.xxx] 
Note: Denominators for percentages are the number of subjects in the Safety population who received both the first and second study vaccination. [x] subjects 
did not get the second dose and are not included in this table. 
* P-value is calculated from McNemar's test for each study arm. 
Table with similar format:  
Table 77: 
Number and Percentage of Subjects Experiencing Solicited Injection Site Events for Dose 1 Compared with Dose 2 by Study 
arm and Age Stratum – Safety Population 


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14.3.1.2 
Unsolicited Adverse Events 
Table 78: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events with 95% Confidence Intervals by 
MedDRA® System Organ Class and Preferred Term, and Study Arm – Safety Population 
 
 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(N=X) 
MedDRA® System 
Organ Class 
MedDRA® 
Preferred Term 
n 
%  
(95% 
CI) 
n 
%  
(95% 
CI) 
n 
%  
(95% 
CI) 
n 
%  
(95% 
CI) 
Any SOC 
Any PT 
x 
xx  
(xx-xx) 
x 
xx  
(xx-xx) 
x 
xx  
(xx-xx) 
x 
xx  
(xx-xx) 
[SOC 1] 
Any PT 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
Note: N = Number of subjects in the Safety population. This table presents number and percentage of subjects. A subject is only counted once per PT. 
 
 
 


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Table 79: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events by MedDRA System Organ Class and 
Preferred Term, Maximum Severity, Relationship, and Study Arm – Safety Population 
MedDRA System Organ Class 
MedDRA Preferred Term 
Any Incidence 
Severity [1] 
Relationship to Treatment [2] 
Mild 
Moderate 
Severe 
Not Related 
Related 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Study Arm 1: 3.75 mcg A/H7N9 + MF59 (N = X) 
All Subjects 
Any SOC 
Any PT 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
[SOC 1] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all study arms] 
Note: N = Number of subjects in the Safety 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. 


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Table 80: 
Number and Percentage of Subjects Experiencing Non-Serious Related Unsolicited Adverse Events by MedDRA System 
Organ Class and Preferred Term, Maximum Severity, and Study Arm – Safety Population 
MedDRA System Organ Class 
MedDRA Preferred Term 
Any Incidence 
Severity [1] 
Mild 
Moderate 
Severe 
n 
% 
n 
% 
n 
% 
n 
% 
Study Arm 1: 3.75 mcg A/H7N9 + MF59 (N=X) 
All Subjects 
Any SOC 
Any PT 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
[SOC 1] 
Any PT 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
[Repeat for all study arms] 
Note: N = Number of subjects in the Safety 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. 
 
 


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Table 81: 
Number and Percentage of Subjects Experiencing Unsolicited Adverse Events Within 21 Days Post Study Vaccination by 
MedDRA System Organ Class and Preferred Term, Day Post Vaccination, and Study Arm – Safety Population 
 
 
Day 1-8 
Post Vac 1 
Day 9-22 
Post Vac 1 
Day 1-22 
Post Vac 1 
Day 1-8 
Post Vac 2 
Day 9-22 
Post Vac 2 
Day 1-22 
Post Vac 2 
Day 1-22  
Post Any 
Vaccination 
MedDRA System Organ Class 
MedDRA Preferred 
Term 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Study Arm 1: 3.75 mcg A/H7N9 + MF59, (N=X) 
All Subjects  
Any SOC 
Any PT 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
[SOC 1] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all study arms] 
Note: N = Number of subjects in the Safety Population. This table presents number and percentage of subjects. For each time period, a subject is only counted once per PT. 
 


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Table 82: 
Number and Percentage of Subjects Experiencing Non-Serious, Related Unsolicited Adverse Events Within 21 Days Post 
Vaccination by MedDRA System Organ Class and Preferred Term, Study Vaccination, and Study Arm – Safety Population 
 
 
Day 1-8 
Post Vac 1 
Day 9-22 
Post Vac 1 
Day 1-22 
Post Vac 1 
Day 1-8 
Post Vac 2 
Day 9-22 
Post Vac 2 
Day 1-22 
Post Vac 2 
Day 1-22 
Post Any 
Vaccination 
MedDRA System Organ Class 
MedDRA Preferred 
Term 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Study Arm 1: 3.75 mcg A/H7N9 + MF59 (N=X) 
All Subjects 
Any SOC 
Any PT 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
[SOC 1] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all study arms] 
Note: N = Number of subjects in the Safety population. This table presents number and percentage of subjects. For each time period, a subject is only counted once per PT. 
 


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Table 83: 
Number of Unsolicited Adverse Events by MedDRA System Organ Class and Preferred Term, Day Post Vaccination, and 
Study Arm – Safety Population 
 
 
Day 1-8 
Post Vac 1 
Day 9-22 
Post Vac 1 
Day 1-22 
Post Vac 1 
Day 1-8 
Post Vac 2 
Day 9-22 
Post Vac 2 
Day 1-22 
Post Vac 2 
Day 1-22 
Post Any 
Vaccination 
MedDRA System Organ Class 
MedDRA Preferred Term 
# of Events 
# of 
Events 
# of Events 
# of Events 
# of Events 
# of Events 
# of Events 
Study Arm 1: 3.75 mcg A/H7N9 + MF59 (N=X) 
All Subjects 
Any SOC 
Any PT 
x 
x 
x 
x 
x 
x 
x 
[SOC 1] 
Any PT 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
[SOC 2] 
Any PT 
 
 
 
 
 
 
 
 
[PT 1] 
 
 
 
 
 
 
 
 
[PT 2] 
 
 
 
 
 
 
 
[Repeat for all study arms] 
Note: N = Number of subjects in the Safety population. This table presents number of events; A subject may be counted multiple times. 
 


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14.3.2 Listings of Serious and Significant Adverse Events 
Table 84: 
Listing of Serious Adverse Events – Safety Population 
[Implementation Note: This listing is included in the table shells document, as it is included in the body of the CSR. If the event is ongoing (no stop 
date), indicate “ongoing” in the “Duration” column. If more than one reason is selected for the reason reported as an SAE, list all reasons in the 
column, separated by a comma. In the “If Not Related, Alternate Etiology” column, merge the 2 data fields for collecting alternate etiology, separate 
by a colon. In the CSR, Subject ID should be USUBJID (not PATID) for purposes of de-identification.] 
Adverse 
Event 
Associated 
with Vac # 
# of Days 
Post 
Associated 
Vac 
(Duration) 
# of 
Days 
Post 
Vac the 
Event 
Became 
Serious 
Reason 
Reported 
as an SAE 
Severity 
Relationship 
to Study 
Treatment 
In Not 
Related, 
Alternative 
Etiology 
Action 
Taken with 
Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
MedDRA 
System 
Organ 
Class 
MedDRA 
Preferred 
Term 
Subject ID: , Study arm: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 
Subject ID: , Study arm: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 


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Table 85: 
Listing of Potentially Immune-Mediated Medical Conditions – Safety Population 
[Implementation Note: This listing is included in the tables section, as it is included in the body of the CSR. If the event is ongoing (no stop date), 
indicate “ongoing” in the “Duration” column. In the “If Not Related, Alternate Etiology” column, merge the 2 data fields for collecting alternate 
etiology, separate by a colon.] 
Adverse 
Event 
Associated 
with Vac # 
# of Days 
Post 
Associated 
Vac 
(Duration) 
SAE? 
Severity 
Relationship 
to Study 
Treatment 
In Not 
Related, 
Alternative 
Etiology 
Action 
Taken 
with 
Study 
Treatment 
Subject 
Discontinued 
Due to AE 
Outcome 
MAAE? 
NOCMC? 
MedDRA 
System 
Organ 
Class 
MedDRA 
Preferred 
Term 
 
Subject ID: , Study arm: , AE Number:  
 
 
 
SAE: No 
Mild 
 
 
 
 
 
 
 
 
 
Comments: 
 
 
 
Subject ID: , Study arm: , AE Number:  
 
 
 
 
 
 
 
 
 
 
 
 
 
Comments: 
 
Tables with similar format: 
Table 86: 
Listing of New Onset Chronic Medical Conditions – Safety Population 
Table 87: 
Listing of Non-Serious, Unsolicited, Moderate or Severe Adverse Events – Safety Population 
 


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14.3.3 Narratives of Deaths, Other Serious and Significant Adverse Events  
(not included in SAP, but this is a placeholder for the CSR) 
 


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14.3.4 Displays of Laboratory Results 
Table 88: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Study Arm – 
All Laboratory Parameters – Safety Population 
Treatment Group 
Study Day 
N 
None 
Mild/ 
Grade 1 
Moderate/ 
Grade 2 
Severe/ 
Grade 3 
Missing 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Study Arm 1  
3.75 mcg A/H7N9 + 
MF59 
Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
Day 22 
 
 
 
 
 
 
 
 
 
 
 
 
Day 29 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all Study 
Arms] 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N = Number of subjects in the Safety population. 
The “Max Post Baseline” rows indicate the maximum severity experienced by each subject at any time point post baseline, including unscheduled 
assessments.  
 
 


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Tables with similar format:  
Table 89: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Study arm – Hemoglobin – Safety Population 
Table 90: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Study arm – Alanine aminotransferase (ALT) – Safety 
Population 
Table 91: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Study arm – Total Bilirubin – Safety Population 
Table 92: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Study arm – Creatinine – Safety Population 
 
 


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Table 93: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Study Arm – White Blood Cells – Safety Population 
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 
% 
Study Arm 1  
3.75 mcg A/H7N9 + 
MF59 
Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Day 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 22 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 29 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity 
Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all Study 
Arms] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: N = Number of subjects in the Safety population. 
The “Max Post Baseline” rows indicate the maximum severity experienced by each subject at any time point post baseline, including unscheduled 
assessments.  
 
Table with similar format: 
 
Table 94: 
Laboratory Results by Parameter, Maximum Severity, Study Day, and Study Arm – Platelets – Safety Population 
 
 


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Table 95: 
Laboratory Summary Statistics of Value and Change from Baseline by Parameter, Study Day, and Study Arm – White Blood 
Cells - Safety Population 
Treatment 
Group 
Study 
Day 
Value 
Change from Baseline 
N 
Mean 
Standard 
Deviation 
Median 
Min, Max 
N 
Mean 
Standard 
Deviation 
Median 
Min, Max 
Study Arm 1  
3.75 mcg 
A/H7N9 + MF59 
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 
[Repeat for all Study Arms] 
N = Number of subjects in the Safety population 
 
Tables with similar format: 
Table 96: 
Laboratory Summary Statistics of Value and Change from Baseline by Parameter, Study Day, and Study Arm – Hemoglobin 
- Safety Population 
Table 97: 
Laboratory Summary Statistics of Value and Change from Baseline by Parameter, Study Day, and Study Arm – Platelets - 
Safety Population 
Table 98: 
Laboratory Summary Statistics of Value and Change from Baseline by Parameter, Study Day, and Study Arm – Alanine 
aminotransferase (ALT) - Safety Population 
Table 99: 
Laboratory Summary Statistics of Value and Change from Baseline by Parameter, Study Day, and Study Arm –  
Total Bilirubin - Safety Population 
Table 100: Laboratory Summary Statistics of Value and Change from Baseline by Parameter, Study Day, and Study Arm – Creatinine - 
Safety Population 
 


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14.3.4.5 
Clinical Laboratory Reference Ranges 
(Placeholder for the CSR) 
 


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14.3.5 Abnormal Laboratory Value Listings (by Subject) 
Table 101: Listing of Abnormal Laboratory Results - Chemistry 
Subject 
ID 
Study Arm 
Sex 
Age 
(years) 
Planned 
Time 
Point 
Actual 
Study 
Day 
Laboratory 
Parameter 
(Units) 
Result 
(Severity) 
Relationship 
to Treatment 
If Not 
Related, 
Alternate 
Etiology 
Action 
Taken with 
Study 
Treatment 
Subject 
Discontinued 
Due to 
Result? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table 102: Listing of Abnormal Laboratory Results - Hematology 
Subject 
ID 
Study Arm 
Sex 
Age 
(years) 
Planned 
Time 
Point 
Actual 
Study 
Day 
Laboratory 
Parameter 
(Units) 
Result 
(Severity) 
Relationship 
to Treatment 
If Not 
Related, 
Alternate 
Etiology 
Action 
Taken with 
Study 
Treatment 
Subject 
Discontinued 
Due to 
Result? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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14.3.6 Displays of Vital Signs 
Table 103: Vital Signs by Assessment, Maximum Severity, Study Day, and Study Arm – Any Assessment - Safety Population 
Treatment Group 
Study Day 
N 
None 
Mild 
Moderate 
Severe 
Missing 
n 
% 
n 
% 
n 
% 
n 
% 
n 
% 
Study Arm 1  
3.75 mcg A/H7N9 + 
MF59 
Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Day 22 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all Study Arms] 
Note: N = Number of subjects in the Safety population. 
The “Max Post Baseline” rows indicate the maximum severity experienced by each subject at any time point post baseline, including unscheduled assessments.  
Table with similar format: 
Table 104: Vital Signs by Assessment, Maximum Severity, Study Day, and Study Arm – Oral Temperature - Safety Population 
 
 


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Table 105: Vital Signs by Assessment, Maximum Severity, Study Day, and Study Arm – Systolic Blood Pressure - Safety Population 
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 
% 
Study Arm 1  
3.75 mcg 
A/H7N9 + 
MF59 
Baseline 
x 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
 
Day 22 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max Severity 
Post Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[Repeat for all Study Arms] 
Note: N = Number of subjects in the Safety population. 
The “Max Post Baseline” rows indicate the maximum severity experienced by each subject at any time point post baseline, including unscheduled assessments.  
Tables with similar format: 
Table 106: Vital Signs by Assessment, Maximum Severity, Study Day, and Study Arm – Diastolic Blood Pressure - Analysis Population 
Table 107: Vital Signs by Assessment, Maximum Severity, Study Day, and Study Arm – Pulse - Safety Population 
 


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14.4 
Summary of Concomitant Medications 
Table 108: Number and Percentage of Subjects with Prior and Concurrent Medications by WHO Drug Classification 
and Study Arm- Safety Population 
WHO Drug Code 
Level 1, Anatomic Group 
WHO Drug Code 
Level 2, Therapeutic 
Subgroup 
Study Arm 1 
3.75 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 2 
7.5 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 3 
15 mcg A/H7N9  
+ MF59 
(N=X) 
Study Arm 4 
15 mcg A/H7N9  
(N=X) 
n 
% 
n 
% 
n 
% 
n 
% 
Any Level 1 Codes 
Any Level 2 Codes 
x 
xx 
x 
xx 
x 
xx 
x 
xx 
[ATC Level 1 - 1] 
Any [ATC 1 – 1] 
 
 
 
 
 
 
 
 
 
[ATC 2 - 1] 
 
 
 
 
 
 
 
 
 
[ATC 2 - 2] 
 
 
 
 
 
 
 
 
 
[ATC 2 - 3] 
 
 
 
 
 
 
 
 
[ATC Level 1 – 2] 
[ATC 2 - 1] 
 
 
 
 
 
 
 
 
 
[ATC 2 - 2] 
 
 
 
 
 
 
 
 
 
[ATC 2 - 3] 
 
 
 
 
 
 
 
 
N= Number of subjects in the Safety population; n=Number of subjects reporting taking at least one medication in the specific WHO Drug Class. 


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APPENDIX 2. FIGURE MOCK-UPS 
LIST OF FIGURES 
Figure 1: 
CONSORT Flow Diagram ........................................................................................ 117 
Figure 2: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody 
against A/Hong Kong/125/2017 (H7N9) by Study Day, and Study Arm - Modified 
Intent to Treat Population .......................................................................................... 118 
Figure 3: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
A/Hong Kong/125/2017 (H7N9) by Study Day, and Study Arm - Per-Protocol 
Population .................................................................................................................. 118 
Figure 4: 
Reverse Cumulative Distribution of Neutralizing Antibody Against A/Hong 
Kong/125/2017 (H7N9) by Study Day, and Study Arm - Modified Intent-to-Treat 
Population .................................................................................................................. 118 
Figure 5: 
Reverse Cumulative Distribution of Neutralizing Antibody against A/Hong 
Kong/125/2017 (H7N9) by Study Day, and Study Arm - Per-Protocol Population .. 118 
Figure 6: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody Against A/Hong 
Kong/125/2017 (H7N9) by Study Day, and Study Arm - Modified Intent-to-Treat 
Population .................................................................................................................. 119 
Figure 7: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody against A/Hong 
Kong/125/2017 (H7N9) by Study Day and Study Arm - Per-Protocol Population ... 119 
Figure 8: 
Geometric Mean Titers of Neutralizing Antibody against A/Hong Kong/125/2017 
(H7N9) Study Day and Study Arm - Modified Intent-to-Treat Population ............... 119 
Figure 9: 
Geometric Mean Titers of Neutralizing Antibody against A/Hong Kong/125/2017 
(H7N9) by Study Day and Study Arm - Per-Protocol Population ............................. 119 
Figure 10: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against A/Hong Kong/125/2017 (H7N9) by Study Day and Study Arm - Modified 
Intent-to-Treat Population ......................................................................................... 120 
Figure 11: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against A/Hong Kong/125/2017 (H7N9) by Study Day and Study Arm - Per-Protocol 
Population .................................................................................................................. 120 
Figure 12: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
A/Shanghai/2/2013 (H7N9) by Study Day and Study Arm - Per-Protocol Population
 ................................................................................................................................... 121 
Figure 13: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
A/Guangdong/17SF003/2016 (H7N9) by Study Day and Study Arm - Per-Protocol 
Population .................................................................................................................. 121 
Figure 14: 
Reverse Cumulative Distribution of Neutralizing Antibody against A/Shanghai/2/2013 
(H7N9) by Study Day and Study Arm - Per-Protocol Population ............................. 121 
Figure 15: 
Reverse Cumulative Distribution of Neutralizing Antibody against 
A/Guangdong/17SF003/2016 (H7N9) by Study Day and Study Arm - Per-Protocol 
Population .................................................................................................................. 121 
Figure 16: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody against 
A/Shanghai/2/2013 (H7N9) by Study Day and Study Arm - Per-Protocol Population
 ................................................................................................................................... 122 
Figure 17: 
Geometric Mean Titers of Neutralizing Antibody against 
A/Guangdong/17SF003/2016 (H7N9) by Study Day and Study Arm - Per-Protocol 
Population .................................................................................................................. 122 


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Figure 18: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody against 
A/Shanghai/2/2013 (H7N9) by Study Day and Study Arm - Per-Protocol Population
 ................................................................................................................................... 122 
Figure 19: 
Geometric Mean Titers of Neutralizing Antibody against 
A/Guangdong/17SF003/2016 (H7N9) by Study Day and Study Arm - Per-Protocol 
Population .................................................................................................................. 122 
Figure 20: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against A/Shanghai/2/2013 (H7N9) by Study Day and Study Arm - Per-Protocol 
Population .................................................................................................................. 123 
Figure 21: 
Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against A/Guangdong/17SF003/2016 (H7N9) by Study Day and Study Arm - Per-
Protocol Population ................................................................................................... 123 
Figure 22: 
Correlation of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 and 
A/Shanghai/2/2013 (H7N9) by Study Day and Study Arm - Per-Protocol Population
 ................................................................................................................................... 123 
Figure 23: 
Correlation of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 and 
A/Guangdong/17SF003/2016 (H7N9) by Study Day and Study Arm - Per-Protocol 
Population .................................................................................................................. 124 
Figure 24: 
Correlation of Neutralizing Antibody Against 2017 A/H7N9 and A/Shanghai/2/2013 
(H7N9) by Study Day and Study Arm - Per-Protocol Population ............................. 124 
Figure 25: 
Correlation of Neutralizing Antibody Against 2017 A/H7N9 and 
A/Guangdong/17SF003/2016 (H7N9) by Study Day and Study Arm - Per-Protocol 
Population .................................................................................................................. 124 
Figure 26: 
Maximum Severity of Solicited Systemic Symptoms per Subject by Day Post Study 
Vaccination – Safety Population ............................................................................... 125 
Figure 27: 
Maximum Severity of Solicited Injection Site Symptoms per Subject by Day Post 
Study Vaccination – Safety Population ..................................................................... 125 
Figure 28: 
Frequency of Unsolicited Adverse Events by MedDRA® System Organ Class and 
Severity – Safety Population ..................................................................................... 126 
Figure 29: 
Incidence of Unsolicited Adverse Events by MedDRA® System Organ Class and 
Severity – Safety Population ..................................................................................... 127 
Figure 30: 
Frequency of Adverse Events by MedDRA® System Organ Class and Relationship to 
Treatment – Safety Population .................................................................................. 128 
Figure 31: 
Incidence of Adverse Events by MedDRA® System Organ Class and Relationship to 
Treatment – Safety Population .................................................................................. 129 
Figure 32: 
Laboratory Results by Scheduled Visits: Mean Changes from Baseline by Laboratory 
Parameter and Study Arm – White Blood Cells - Safety Population ........................ 130 
Figure 33: 
Laboratory Summary Statistics of Change from Baseline by Parameter, Maximum 
Severity, Study Day, and Study Arm – Hemoglobin - Safety Population ................. 130 
Figure 34: 
Laboratory Summary Statistics of Change from Baseline Results by Parameter, 
Maximum Severity, Study Day, and Study Arm – Platelets - Safety Population ...... 130 
Figure 35: 
Laboratory Summary Statistics of Change from Baseline by Parameter, Maximum 
Severity, Study Day, and Study Arm – Alanine Aminotransferase (ALT) - Safety 
Population .................................................................................................................. 130 
Figure 36: 
Laboratory Summary Statistics of Change from Baseline Results by Parameter, 
Maximum Severity, Study Day, and Study Arm – Total Bilirubin - Safety Population
 ................................................................................................................................... 131 
Figure 37: 
Laboratory Summary Statistics of Change from Baseline Results by Parameter, 
Maximum Severity, Study Day, and Study Arm – Creatinine - Safety Population ... 131 
 


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10.1 
Disposition of Subjects Figures 
Figure 1: 
CONSORT Flow Diagram 
 
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 Study Arm 2 (n=x) 
♦Received allocated intervention (n=x) 
♦Did not receive allocated intervention 
(n=x) 
[Reason 1] (x), [Reason 2] (x) 
Allocated to Study Arm 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) 
Discontinued Intervention (n=x) 
♦[Reason 1] (x), [Reason 2] (x) 
Early Termination (n=32) 
♦[Reason 1] (x), [Reason 2] (x) 
Analysed for immunogenicity (n=x) 
♦Excluded from immuno analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for safety (n=x) 
♦Excluded from safety analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analysed for immunogenicity (n=x) 
♦Excluded from immuno analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for safety (n=x) 
♦Excluded from safety analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Allocated to Study Arm 1 (n=x) 
♦Received allocated intervention (n=x) 
♦Did not receive allocated intervention 
(n=x) 
[Reason 1] (x), [Reason 2] (x) 
Discontinued Intervention (n=x) 
♦[Reason 1] (x), [Reason 2] (x) 
Early Termination (n=32) 
♦[Reason 1] (x), [Reason 2] (x) 
Allocated to Study Arm 4 (n=x) 
♦ Received allocated intervention (n=x) 
♦ Did not receive allocated intervention 
(n=x) 
[Reason 1] (x), [Reason 2] (x) 
Discontinued Intervention (n=x) 
♦ [Reason 1] (x), [Reason 2] (x) 
Early Termination (n=32) 
♦ [Reason 1] (x), [Reason 2] (x) 
Analysed for immunogenicity (n=x) 
♦ Excluded from immuno analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 
Analyzed for safety (n=x) 
♦ Excluded from safety analyses (n=x) 
[Reason 1] (x), [Reason 2] (x) 


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14.2.2 Immunogenicity Figures 
Figure 2: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody 
against A/Hong Kong/125/2017 (H7N9) by Study Day, and Study Arm - Modified 
Intent to Treat Population 
[Implementation Note: A generic sample figure is shown below. The RCD curves should be presented 
in a single figure with separate panels for each study day (Baseline, Day 8, Day 22, Day 29, Day 43, 
Day 202). Figures generated for preliminary report will include data from all available visits at the time 
of report generation. Visit labels should be included in the panel headers. Within each panel individual 
curves should be used for each study arm (four curves).] 
 
 
 
Figures with similar format: 
Figure 3: 
Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
A/Hong Kong/125/2017 (H7N9) by Study Day, and Study Arm - Per-Protocol 
Population 
Figure 4: 
Reverse Cumulative Distribution of Neutralizing Antibody Against A/Hong 
Kong/125/2017 (H7N9) by Study Day, and Study Arm - Modified Intent-to-Treat 
Population 
Figure 5: 
Reverse Cumulative Distribution of Neutralizing Antibody against A/Hong 
Kong/125/2017 (H7N9) by Study Day, and Study Arm - Per-Protocol Population 
 


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Figure 6: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody Against A/Hong 
Kong/125/2017 (H7N9) by Study Day, and Study Arm - 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 study arm. Each study arm 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 7: 
Geometric Mean Titers of Hemagglutination Inhibition Antibody against A/Hong 
Kong/125/2017 (H7N9) by Study Day and Study Arm - Per-Protocol Population 
Figure 8: 
Geometric Mean Titers of Neutralizing Antibody against A/Hong Kong/125/2017 
(H7N9) Study Day and Study Arm - Modified Intent-to-Treat Population 
Figure 9: 
Geometric Mean Titers of Neutralizing Antibody against A/Hong Kong/125/2017 
(H7N9) by Study Day and Study Arm - Per-Protocol Population 
 


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Figure 10: Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against A/Hong Kong/125/2017 (H7N9) by Study Day and Study Arm - Modified 
Intent-to-Treat Population 
[Implementation Note: A generic sample figure is shown below. The scatter plots should be presented 
in a single figure with separate panels for each visit (Baseline, D8, D22, D29, D43, D202. Visit labels 
should be included in the panel header. Within each panel distinct marker types and colors should be 
used to indicate the study arms, with treatment group labels included in a legend. ). Each study arm 
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 11: Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against A/Hong Kong/125/2017 (H7N9) by Study Day and Study Arm - Per-Protocol 
Population 
 
 


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Figure 12: Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
A/Shanghai/2/2013 (H7N9) by Study Day and Study Arm - Per-Protocol Population 
[Implementation Note: A generic sample figure is shown below. The RCD curves should be presented 
in a single figure with separate panels for each study day (Baseline[Day1], Day 8, Day 22, Day 29, Day 
43, Day 202. Visit labels should be included in the panel headers. Within each panel individual curves 
should be used for each study arm (four curves). Each study arm should have a separate color.] 
[Implementation Note: repeat for all heterologous strains] 
 
 
Figure with Similar Format: 
Figure 13: Reverse Cumulative Distribution of Hemagglutination Inhibition Antibody against 
A/Guangdong/17SF003/2016 (H7N9) by Study Day and Study Arm - Per-Protocol 
Population 
Figure 14: Reverse Cumulative Distribution of Neutralizing Antibody against 
A/Shanghai/2/2013 (H7N9) by Study Day and Study Arm - Per-Protocol Population  
Figure 15: Reverse Cumulative Distribution of Neutralizing Antibody against 
A/Guangdong/17SF003/2016 (H7N9) by Study Day and Study Arm - Per-Protocol 
Population 
 
 


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Figure 16: Geometric Mean Titers of Hemagglutination Inhibition Antibody against 
A/Shanghai/2/2013 (H7N9) by Study Day and Study Arm - Per-Protocol Population 
[Implementation Note: A generic sample figure is shown below. Planned Study Day is plotted along the 
x-axis, with visit labels as tick labels. Titer is plotted on the y-axis on the log-10 scale. GMT should be 
plotted at each visit with upper and lower error bars for the 95% CI for each treatment group with 
different marker shapes/colors for each study arm.] 
[Implementation Note: repeat for all heterologous strains] 
 
Figures with similar format: 
Figure 17: Geometric Mean Titers of Neutralizing Antibody against 
A/Guangdong/17SF003/2016 (H7N9) by Study Day and Study Arm - Per-Protocol 
Population  
Figure 18: Geometric Mean Titers of Hemagglutination Inhibition Antibody against 
A/Shanghai/2/2013 (H7N9) by Study Day and Study Arm - Per-Protocol Population 
Figure 19: Geometric Mean Titers of Neutralizing Antibody against 
A/Guangdong/17SF003/2016 (H7N9) by Study Day and Study Arm - Per-Protocol 
Population 
 


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Figure 20: Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against A/Shanghai/2/2013 (H7N9) by Study Day and Study Arm - Per-Protocol 
Population 
[Implementation Note: A generic sample figure is shown below. The scatter plots should be presented 
in a single figure with separate panels for each visit (Baseline, D8, D22, D29, D43, D202. Visit labels 
should be included in the panel header. Within each panel distinct marker types and colors should be 
used to indicate the study arms, with treatment group labels included in a legend. Each study arm 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)”.] 
[Implementation Note: repeat for all heterologous strains] 
 
 
Figures with similar format (may repeat as needed for additional strains): 
Figure 21: Correlation of Hemagglutination Inhibition Antibody and Neutralizing Antibody 
Against A/Guangdong/17SF003/2016 (H7N9) by Study Day and Study Arm - Per-
Protocol Population 
Figure 22: Correlation of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 and 
A/Shanghai/2/2013 (H7N9) by Study Day and Study Arm - Per-Protocol Population  


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Figure 23: Correlation of Hemagglutination Inhibition Antibody Against 2017 A/H7N9 and 
A/Guangdong/17SF003/2016 (H7N9) by Study Day and Study Arm - Per-Protocol 
Population 
Figure 24: Correlation of Neutralizing Antibody Against 2017 A/H7N9 and A/Shanghai/2/2013 
(H7N9) by Study Day and Study Arm - Per-Protocol Population 
Figure 25: Correlation of Neutralizing Antibody Against 2017 A/H7N9 and 
A/Guangdong/17SF003/2016 (H7N9) by Study Day and Study Arm - Per-Protocol 
Population 
 


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14.3.1 Safety Figures 
14.3.1.1 Solicited Adverse Events 
Figure 26: Maximum Severity of Solicited Systemic Symptoms per Subject by Day Post Study 
Vaccination – Safety Population 
[Implementation Note: A Generic figure is shown below. A vertical bar chart should be presented in 3 
image files with separate panels for each study arm and study vaccination (4 rows (study arms) x 2 
columns (vaccination #)). Axes should be labeled as follows: x-axis label: Study Day, y-axis label: 
Percentage of Subjects (%). The study arms should be indicated in the panel headers including “(N=X)”, 
where N = the number of subjects in the in the Safety Population who received the relevant dose. 
Subjects are counted at most once at the maximum severity across all systemic events reported for the 
specified time point] 
 
 
Figure with similar format: 
Figure 27: Maximum Severity of Solicited Injection Site Symptoms per Subject by Day Post 
Study Vaccination – Safety Population 
 


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14.3.1.2 Unsolicited Adverse Events 
Figure 28: Frequency of Unsolicited Adverse Events by MedDRA® System Organ Class 
and Severity – Safety Population 
[Implementation Note: A Generic figure is shown below. This figure includes all unsolicited events 
across all vaccinations. A horizontal bar chart should be presented in 3 image files with separate panels 
for each study arm (4 columns (study arms)). Axes should be labeled as follows: y-axis label: System 
Organ Class, x-axis label: Number of Events. The study arms should be indicated in the panel headers 
including “(N=X)”, where N = the number of subjects in the in the Safety Population. The y-axis should 
present all SOCs reported by at least 1 subject and an “All Events” category. Y-axis should be sorted 
with “All Events first, then in decreasing order of total incidence] 
 
 


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Figure 29: Incidence of Unsolicited Adverse Events by MedDRA® System Organ Class 
and Severity – Safety Population 
[Implementation Note: A Generic figure is shown below. This figure includes all unsolicited events 
across all vaccinations. A horizontal bar chart should be presented in 2 image files per each vaccination 
with separate panels for each study arm (4 columns). Axes should be labeled as follows: y-axis label: 
System Organ Class, x-axis label: Percentage of Subjects (%). The study arms should be indicated in 
the panel headers including “(N=X)”, where N = the number of subjects in the in the Safety Population. 
Subjects are counted at most once at the maximum severity across for any events in the applicable SOC. 
The y-axis should present all SOCs reported by at least 1 subject and an “All Events” category. Y-axis 
should be sorted with “All Events” first then in decreasing order of total incidence]  
 
 
 


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Figure 30: Frequency of Adverse Events by MedDRA® System Organ Class and Relationship to 
Treatment – Safety Population 
[Implementation Note: A generic sample figure is shown below. This figure includes all unsolicited 
events across all vaccinations. A horizontal bar chart should be presented in 2 image files per each 
vaccination with separate panels for each study arm (4 columns). Axes should be labeled as follows: y-
axis label: System Organ Class, x-axis label: Number of Events. The study arms should be indicated in 
the panel headers including “(N=X)”, where N = the number of subjects in the in the Safety Population. 
The y-axis should present all SOCs reported by at least 1 subject and an “All Events” category. Y-axis 
should be sorted with “All Events first then in decreasing order of total frequency] 
 
 


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Figure 31: Incidence of Adverse Events by MedDRA® System Organ Class and Relationship to 
Treatment – Safety Population 
[Implementation Note: A Generic figure is shown below. This figure includes all unsolicited events 
across all vaccinations. A horizontal bar chart should be presented in 2 image files per each vaccination 
with separate panels for each study arm (4 columns). Axes should be labeled as follows: y-axis label: 
System Organ Class, x-axis label: Percentage of Subjects (%). The study arms should be indicated in 
the panel headers including “(N=X)”, where N = the number of subjects in the in the Safety Population. 
Subjects are counted at most once at the maximum relationship (related >not-related) across for any 
events in the applicable SOC. The y-axis should present all SOCs reported by at least 1 subject and an 
“All Events” category. Y-axis should be sorted with “All Events first, then in decreasing order of total 
incidence across groups]  
 
 


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14.3.5 Displays of Laboratory Results 
Figure 32: Laboratory Results by Scheduled Visits: Mean Changes from Baseline by 
Laboratory Parameter and Study Arm – White Blood Cells - Safety Population 
[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 study arm (4 rows) with a box plot shown for each 
post-baseline study day that labs are drawn (D8, D22, D29). Y-axis should be labeled “[Parameter] 
Change from baseline ([units]). Repeat for all clinical laboratory parameters: WBC, Hgb, PLT, ALT, T. 
Bili, Cr] 
 
Figures with similar format: 
Figure 33: Laboratory Summary Statistics of Change from Baseline by Parameter, Maximum 
Severity, Study Day, and Study Arm – Hemoglobin - Safety Population 
Figure 34: Laboratory Summary Statistics of Change from Baseline Results by Parameter, 
Maximum Severity, Study Day, and Study Arm – Platelets - Safety Population 
Figure 35: Laboratory Summary Statistics of Change from Baseline by Parameter, Maximum 
Severity, Study Day, and Study Arm – Alanine Aminotransferase (ALT) - Safety 
Population 
 


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Figure 36: Laboratory Summary Statistics of Change from Baseline Results by Parameter, 
Maximum Severity, Study Day, and Study Arm – Total Bilirubin - Safety 
Population 
Figure 37: Laboratory Summary Statistics of Change from Baseline Results by Parameter, 
Maximum Severity, Study Day, and Study Arm – Creatinine - Safety Population 
 


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APPENDIX 3. LISTINGS MOCK-UPS 
 
LIST OF LISTINGS 
Listing 1: 
16.1.6 - Listing of Subjects Receiving Investigational Product .................................. 133 
Listing 2: 
16.2.1 - Early Terminations or Discontinued Subjects ............................................... 134 
Listing 3: 
16.2.2.1 - Subject-Specific Protocol Deviations ......................................................... 135 
Listing 4: 
16.2.2.2 - Non-Subject-Specific Protocol Deviations ................................................. 136 
Listing 5: 
16.2.3 - Subjects Excluded from Analysis Populations .............................................. 137 
Listing 6: 
16.2.4.1 - Demographics Data ..................................................................................... 138 
Listing 7: 
16.2.4.2 – Pre-Existing and Concurrent Medical Conditions ...................................... 139 
Listing 8: 
16.2.6.1 - Individual HAI Response Data ................................................................... 141 
Listing 9: 
16.2.6.2 - Individual Neut Antibody Response Data .................................................. 141 
Listing 10: 
16.2.7.1 - Solicited Events – Systemic Symptoms ...................................................... 142 
Listing 11: 
16.2.7.2 - Solicited Events – Local Symptoms ........................................................... 143 
Listing 12: 
16.2.7.3 - Unsolicited Adverse Events ........................................................................ 144 
Listing 13: 
16.2.8.1 - Clinical Laboratory Results – Chemistry .................................................... 145 
Listing 14: 
16.2.8.2 - Clinical Laboratory Results – Hematology ................................................. 146 
Listing 15: 
16.2.9.1 - Vital Signs ................................................................................................... 147 
Listing 16: 
16.2.9.2 - Physical Exam Findings .............................................................................. 148 
Listing 17: 
16.2.10 - Concomitant Medications ............................................................................ 149 
Listing 18: 
16.2.11.1 - Pregnancy Reports – Maternal Information .............................................. 150 
Listing 19: 
16.2.11.2 - Pregnancy Reports – Gravida and Para ..................................................... 151 
Listing 20: 
16.2.11.3 - Pregnancy Reports – Live Birth Outcomes ............................................... 151 
Listing 21: 
16.2.11.4 - Pregnancy Reports – Still Birth Outcomes ............................................... 151 
Listing 22: 
16.2.11.5 - Pregnancy Reports – Spontaneous, Elective, or Therapeutic Abortion 
Outcomes ................................................................................................. 152 
 
 
 
 


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


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16.2 
Database Listings by Subject 
16.2.1 Discontinued Subjects 
Listing 2: 
16.2.1 - Early Terminations or Discontinued Subjects 
[Implementation Note: Category will be either “Early Termination” or “Treatment Discontinuation.” In the “Reason” column, concatenate any 
“specify” fields, including AE number and DV number.] 
Subject ID 
Study Arm 
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 
Study Arm 
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.] 
Study Arm 
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 
Study Arm 
Sex 
Age at Enrollment 
(years) 
Ethnicity 
Race 
BMI 
Seasonal 
Influenza 
Received 
(2016-2017) 
Seasonal 
Influenza 
Received 
(2017-2018) 
Seasonal 
Influenza 
Received 
(2018-2019) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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


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


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16.2.6 Individual Immunogenicity Response Data 
Listing 8: 
16.2.6.1 - Individual HAI Response Data 
Subject ID 
Study Arm 
Planned Time Point 
Actual Study Day 
Assay 
Strain 
Titer Replicate 1 
Titer Replicate 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 9: 
16.2.6.2 - Individual Neut Antibody Response Data 
Subject ID 
Study Arm 
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 
Study Arm 
Vac Number 
Post Vac Day 
Assessmenta 
Symptom 
Severity 
Attributed to 
Alternate 
Etiology?b 
Alternate 
Etiology 
 
 
 
 
MA 
 
 
 
 
 
 
 
 
Clinic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a MA = Data reported by subject on the Memory Aid and reviewed by clinic staff and reported in Solicited Events eCRF. 
Clinic = Data collected by clinic staff during physical exam or symptom assessment (treatment administration record, in-clinic assessment, etc.) 
b Grade 3 events only. 
 


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Listing 11: 16.2.7.2 - Solicited Events – Injection Site Symptoms 
Subject ID 
Study Arm 
Vac Number 
Post Vac Day 
Assessmenta 
Symptom 
Severity 
 
 
 
 
MA 
 
 
 
 
 
 
Clinic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a MA = Data reported by subject on the Memory Aid and reviewed by clinic staff and reported in Solicited Events eCRF. 
Clinic = Data collected by clinic staff during physical exam or symptom assessment (treatment administration record, in-clinic assessment, etc.) 
 
 


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


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16.2.8 Individual Laboratory Measurements 
Listing 13: 16.2.8.1 - Clinical Laboratory Results – Chemistry 
[Implementation Note: These listings (for hematology and chemistry) include all laboratory results, scheduled and unscheduled. These listings are 
not color-coded, but the severity should be included in parentheses after the result for abnormal results, e.g., 16.2 (Mild). The “extra” fields that are 
completed for abnormal results are not included in this listing; they are included in the listing of abnormal laboratory results that is included in the 
table shells.] 
Subject ID 
Study Arm 
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 – Hematology 
Subject ID 
Study Arm 
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 
Study Arm  
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 
Study Arm 
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 
Study Arm 
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 
Study Arm 
Pregnancy 
Number 
Study Day 
Corresponding 
to Estimated 
Date of 
Conception 
Source of 
Maternal 
Information 
Pregnancy 
Status 
Mother’s 
Pre-
Pregnancy 
BMI 
Mother’s 
Weight 
Gain 
During 
Pregnancy 
Tobacco, 
Alcohol, or 
Drug Use 
During 
Pregnancy? 
Medications 
During 
Pregnancy? 
Maternal 
Complications 
During 
Pregnancy? 
Maternal 
Complications 
During Labor, 
Delivery, or 
Post-Partum? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Maternal Complications are included in the Adverse Event listing. Medications taken during pregnancy are included in the Concomitant Medications 
Listing. 
 


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Listing 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. 
 
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? 
 
 
 
 
 
 
 
 
 
 
 
 


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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