A Phase 3, Randomized, Observer-blind, Multicenter Study to Evaluate the Efficacy, Immunogenicity and Safety of Seqirus' Cell-Based Quadrivalent Subunit Influenza Virus Vaccine (QIVc) Compared to a Non-Influenza Vaccine When Administrated in Healthy Subjects Aged 6 Months Through 47 Months
Phase: PHASE3
Conditions: Influenza, Human
Sponsor: Seqirus

Seqirus 
Confidential 
Protocol V130_14 
03 SEP 20 Version 3.0 
 
Page 1 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
 
 
 
 
CLINICAL STUDY PROTOCOL V130_14 
Final Version 3.0, dated 03 SEPTEMBER 2020 
A Phase III, Randomized, Observer-blind, Multicenter Study to Evaluate the 
Efficacy, Immunogenicity and Safety of Seqirus’ Cell-Based Quadrivalent Subunit 
Influenza Virus Vaccine (QIVc) Compared to a Non-Influenza Vaccine when 
Administrated in Healthy Subjects aged 6 Months through 47 Months 
 
A Phase III Efficacy Study with QIVc in Pediatric Subjects 
 
EudraCT number 2018-001857-29 
IND number 15744 
 
 
 
 
Property of Seqirus* 
Confidential 
May not be used, divulged, published or otherwise disclosed without written 
 consent of Seqirus 
*“Seqirus” includes all legal entities under which the company operates 

Seqirus 
Confidential 
Protocol V130_14 
03 SEP 20 Version 3.0 
 
Page 2 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
TABLE OF CONTENTS 
TABLE OF CONTENTS ..................................................................................................... 2 
PROTOCOL SYNOPSIS V130_14 ..................................................................................... 6 
LIST OF ABBREVIATIONS ............................................................................................ 30 
LIST OF DEFINITIONS ................................................................................................... 32 
1. 
BACKGROUND AND RATIONALE .................................................................... 35 
1.1 
Background .......................................................................................................... 35 
1.2  Potential Risks and Benefits ................................................................................ 36 
1.3 
Rationale .............................................................................................................. 37 
2. 
OBJECTIVES ........................................................................................................... 38 
2.1 
Primary Objective(s) ............................................................................................ 38 
2.2 
Secondary Objective(s) ........................................................................................ 38 
2.3 
Exploratory Objective(s) ..................................................................................... 39 
3. 
STUDY DESIGN ..................................................................................................... 40 
3.1 
Overview of Study Design ................................................................................... 40 
3.2 
Study Period ......................................................................................................... 43 
3.3 
Blinding Procedures ............................................................................................. 43 
3.3.1 Subjects 6 through 11 months old at enrollment ............................................. 43 
3.4 
Data Collection .................................................................................................... 44 
3.4.1 Data Collected from Subjects ....................................................................... 44 
3.4.2 Tools Used for Data Collection .................................................................... 44 
3.5 
Collection of Clinical Specimens ........................................................................ 46 
3.6 
Stopping/Pausing Guidelines ............................................................................... 47 
3.7 
Data Monitoring Committee ................................................................................ 47 
3.8 
Premature Withdrawal from Study ...................................................................... 48 
3.9 
End of Study ........................................................................................................ 51 
4. 
SELECTION OF STUDY POPULATION .............................................................. 52 
4.1 
Inclusion Criteria ................................................................................................. 52 
4.2 
Exclusion Criteria ................................................................................................ 52 

Seqirus 
Confidential 
Protocol V130_14 
03 SEP 20 Version 3.0 
 
Page 3 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
4.3 
Criteria for Delay of Vaccination ........................................................................ 54 
5. 
STUDY PROCEDURES .......................................................................................... 55 
5.1 
Pre-vaccination Procedure(s) ............................................................................... 56 
5.1.1 Informed Consent ......................................................................................... 56 
5.1.2 Screening ...................................................................................................... 57 
5.1.3 Enrolment ..................................................................................................... 58 
5.1.4 Randomization .............................................................................................. 58 
5.1.5  Blood draw.................................................................................................... 59 
5.2 
Procedure(s) related to Vaccination ..................................................................... 59 
5.2.1  Vaccination ................................................................................................... 60 
5.2.2  Subject Diary Card Dispense and Training .................................................. 60 
5.2.3  Schedule the next study activity ................................................................... 61 
5.2.4 Diary Reminder Calls ................................................................................... 61 
5.2.5  ILI Symptom Assessment and Documentation Training ............................. 62 
5.3 
Post-vaccination Visit(s) ...................................................................................... 62 
5.3.1 Follow-up Clinic Visit .................................................................................. 62 
5.3.2 Safety Follow-up Visit .................................................................................. 63 
5.4 
Procedure(s) related to Protocol Defined ILI episodes ........................................ 64 
5.4.1  ILI Reminder Calls ....................................................................................... 64 
5.4.2  Unscheduled Visit(s) .................................................................................... 64 
5.4.3  ILI Follow-up Call ........................................................................................ 65 
5.5 
Study Completion ................................................................................................ 66 
5.5.1 Early Termination Visit ................................................................................ 67 
5.5.2 Countries without MenC market authorization ............................................... 68 
6. 
TREATMENT OF SUBJECTS ................................................................................ 69 
6.1 
Study Vaccine(s) .................................................................................................. 69 
6.2 
Vaccine Preparation and Administration ............................................................. 70 
6.3 
Vaccine Administration Error or Overdose of Vaccine ...................................... 71 
6.4 
Prior and Concomitant Medications and Vaccines .............................................. 72 

Seqirus 
Confidential 
Protocol V130_14 
03 SEP 20 Version 3.0 
 
Page 4 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
6.5 
Vaccine Supply, Labeling, Storage and Tracking ............................................... 73 
7. 
ASSESSMENTS ...................................................................................................... 76 
7.1 
Safety Assessment ............................................................................................... 76 
7.1.1 Solicited Adverse Events .............................................................................. 76 
7.1.2 Unsolicited Adverse Events .......................................................................... 79 
7.1.3 Evaluation of Adverse Events ...................................................................... 79 
7.1.4 Serious Adverse Events ................................................................................ 81 
7.1.5 Methods for Recording Adverse Events and Serious Adverse Events ......... 83 
7.1.6 Safety Laboratory Measurements ................................................................. 84 
7.2 
Efficacy Assessment ............................................................................................ 84 
7.3 
Immunogenicity Assessment ............................................................................... 85 
8. 
STATISTICAL CONSIDERATIONS ..................................................................... 86 
8.1 
Endpoints ............................................................................................................. 86 
8.1.1 Primary Endpoint(s)...................................................................................... 86 
8.1.2 Secondary Endpoint(s).................................................................................. 86 
8.1.3 Exploratory Endpoint(s) ............................................................................... 88 
8.2 
Success Criteria ................................................................................................... 88 
8.2.1 Success Criteria for Primary Objective(s) .................................................... 88 
8.2.2 Success Criteria for Secondary Objective(s) ................................................ 88 
8.3 
Analysis Sets ........................................................................................................ 89 
8.3.1 All Enrolled Set ............................................................................................ 89 
8.3.2 All Exposed Set ............................................................................................ 89 
8.3.3 Safety Set ...................................................................................................... 89 
8.3.4 Full Analysis Set (FAS) Efficacy/Immunogenicity Set................................ 89 
8.3.5 Per Protocol (PP) Set Efficacy/Immunogenicity Set .................................... 90 
8.3.6 Other Analysis Sets....................................................................................... 90 
8.3.7 Subgroups ..................................................................................................... 90 
8.3.8 Protocol Deviations ...................................................................................... 91 
8.4 
Statistical Analysis Plan ...................................................................................... 92 

Seqirus 
Confidential 
Protocol V130_14 
03 SEP 20 Version 3.0 
 
Page 5 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
8.4.1 Analysis of Demographic and Baseline Characteristics ............................... 92 
8.4.2 Analysis of Primary Objective(s) ................................................................. 92 
8.4.3 Analysis of Secondary Objective(s) ............................................................. 95 
8.4.4 Analysis of Exploratory Objectives .............................................................. 99 
8.5 
Sample Size and Power Considerations of Multiple Primary and Secondary 
Objectives ............................................................................................................ 99 
8.6 
Interim Analysis ................................................................................................. 101 
9. 
SOURCE DOCUMENTATION, STUDY MONITORING AND AUDITING .... 103 
9.1 
Source Documentation ....................................................................................... 103 
9.2 
Study Monitoring, Auditing and Source Data Verification ............................... 104 
10. 
DATA MANAGEMENT ....................................................................................... 106 
10.1 Data Entry and Management ............................................................................. 106 
10.2 Data Clarification ............................................................................................... 106 
10.3 Data Protection .................................................................................................. 106 
11. 
RECORD RETENTION ........................................................................................ 107 
12. 
USE OF INFORMATION AND PUBLICATION ................................................ 108 
13. 
ETHICAL CONSIDERATIONS ........................................................................... 109 
13.1 Regulatory and Ethical Compliance .................................................................. 109 
13.2 Informed Consent Procedures ............................................................................ 109 
13.3 Responsibilities of the Investigator and IRB/EC ............................................... 110 
13.4 Protocol Amendments ....................................................................................... 111 
14. 
REFERENCE LIST ................................................................................................ 112 
 

Seqirus 
Confidential 
Protocol V130_14 
03 SEP 20 Version 3.0 
 
Page 6 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
PROTOCOL SYNOPSIS V130_14  
Name of Sponsor: 
Seqirus 
 
Protocol number: 
V130_14 
Generic name of study vaccine(s): 
Cell-Based Quadrivalent Subunit 
Influenza Virus Vaccine (QIVc) 
Non-Influenza Vaccine 
Title of Study:  
A Phase III, Randomized, Observer-blind, Multicenter Study to Evaluate the Efficacy, 
Immunogenicity and Safety of Seqirus’ Cell-Based Quadrivalent Subunit Influenza 
Virus Vaccine (QIVc) Compared to a Non-Influenza Vaccine when Administrated in 
Healthy Subjects aged 6 Months through 47 Months 
Study Period: Until end of influenza 
season but at least 180 days after last 
vaccination date (approximately six to ten 
months) 
Clinical Phase: Phase III  
Background and Rationale: 
Influenza is an infectious disease caused by the influenza virus, an orthomyxovirus with 
two clinically relevant types (Type A and B). Influenza Type A/H1N1, A/H3N2, and 
Type B/Victoria and B/Yamagata strains have circulated and caused disease in humans 
on a global basis since 1977 (Fiore, 2010), with a high susceptibility to severe influenza 
in children (Izurieta, 2000) (Bourgeois, 2006). Children aged < 5 years, and particularly 
those < 2 years of age, are at high risk of infection and are a priority for annual seasonal 
influenza vaccination throughout the world (WHO, 2012) (AAP, 2016). With 
vaccination as the recommended method to prevent influenza, both childhood influenza 
disease burden and community viral transmission could be reduced (Mertz, 2016). 
One of the challenges of protecting children against influenza is providing an influenza 
vaccine with an antigenic match against the circulating strains in a given influenza 
season. Since 1983, two evolutionarily distinct lineages of influenza B viruses have co-
circulated in the human population globally (Biere, 2010) and influenza B viruses 
account for roughly 20% of total influenza cases in all regions of the world (Ciani, 
2015). As only one B lineage is selected for inclusion in current trivalent influenza 
vaccines (TIV) and in the absence of proven cross protection between the two lineages 
(Peltola, 2003) (Hu, 2004), there is the risk of a mismatch for the influenza B strain 
(Couch, 2007) (Belshe, 2010) (Orsi, 2018). Since patients infected with influenza B are 

Seqirus 
Confidential 
Protocol V130_14 
03 SEP 20 Version 3.0 
 
Page 7 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Name of Sponsor: 
Seqirus 
 
Protocol number: 
V130_14 
Generic name of study vaccine(s): 
Cell-Based Quadrivalent Subunit 
Influenza Virus Vaccine (QIVc) 
Non-Influenza Vaccine 
usually younger than patients infected with influenza A, the effectiveness of vaccination 
in children seems more dependent on adequate matching (Jayasundara, 2014) (Caini, 
2015) (Orsi, 2018). To address this problem, quadrivalent influenza vaccines (QIV) 
have been developed containing B strains from both lineages. Although results show 
benefits of QIV vaccination in adults, results from randomized controlled trials in 
children immunized with QIV, are scarce (Claeys, 2018) (Pepin, 2017).  
 
A second challenge is designing a study that captures the clinically relevant outcomes of 
influenza rather than mild upper respiratory tract illness. Parents are most likely to seek 
medical help for children who have symptoms of lower respiratory tract disease, high 
temperature or earache (Saunders, 2003). Studies that do not differentiate these 
manifestations of influenza from mild illness cannot assess the effectiveness of the 
vaccine in attenuating illness and therefore may undervalue its benefit (Jain, 2013) 
(Ambrose, 2014). 
 
Seqirus’ quadrivalent (QIVc) Flucelvax Quadrivalent/ Flucelvax Tetra, is a cell based 
quadrivalent inactivated subunit influenza vaccine prepared from virus propagated in 
Madin Darby Canine Kidney (MDCK) cells, and approved by the FDA for use in 
children aged 4 years and older. As a quadrivalent vaccine, QIVc is formulated to 
contain two influenza A strains and two influenza B strains updated annually as 
recommended by the World Health Organization (WHO) for a specific influenza 
season. A shift from eggs to cell culture has several advantages, for example it avoids 
the risk of egg-adaptive mutations in the HA protein (Lambert, 2010).  
 
The aim of this study is to evaluate the efficacy of QIVc in the prevention of RT-PCR 
confirmed influenza A or B disease in children 6 through 47 months of age, compared 
to a non-influenza vaccine. Efficacy data from all planned influenza seasons will be 
combined. By successfully demonstrating that QIVc decreases influenza disease in this 
age group, it will have the potential to play an important role in the prevention of 
influenza worldwide. 
Study Objectives: Efficacy will be evaluated in all subjects in association with first 
occurrence of influenza-like illness (ILI) symptoms occurring > 14 days after last 

Seqirus 
Confidential 
Protocol V130_14 
03 SEP 20 Version 3.0 
 
Page 8 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Name of Sponsor: 
Seqirus 
 
Protocol number: 
V130_14 
Generic name of study vaccine(s): 
Cell-Based Quadrivalent Subunit 
Influenza Virus Vaccine (QIVc) 
Non-Influenza Vaccine 
vaccination and until the end of the influenza season in subjects 6 months through 47 
months of age at enrollment. 
Influenza-like illness (ILI) is defined by the presence of a temperature ≥ 37.8°C (≥ 
100.0°F) and at least one of the following symptoms on the same day: cough, sore 
throat, nasal congestion, rhinorrhea, earache or ear discharge. 
Moderate-to-severe ILI episode is defined as an ILI episode complicated by one of the 
following: physician confirmed lower respiratory tract illness, physician confirmed 
acute otitis media, or hospitalization in the Intensive Care Unit (ICU), physician-
diagnosed serious extra-pulmonary complication of influenza or supplemental oxygen 
requirement for more than 8 hours. 
Primary Efficacy Objectives:  
1) To demonstrate the absolute vaccine efficacy of QIVc versus a non-influenza 
vaccine to prevent at least one of the following:  
a) RT-PCR confirmed illness caused by any influenza Type A and/or Type B virus, 
regardless of antigenic match.  
b) Culture confirmed illness caused by influenza virus strains antigenically matched to 
the influenza strains selected for the seasonal influenza vaccine. 
Secondary Efficacy Objectives: 
Objectives evaluating QIVc compared to a non-influenza vaccine: 
2) Prevention of culture confirmed illness caused by influenza virus strains 
antigenically dissimilar to the influenza strains selected for the seasonal vaccine. 
3) Prevention of culture confirmed illness caused by any Type A and/or Type B virus. 
4) Prevention of RT-PCR confirmed moderate-to-severe influenza caused by any 
influenza Type A and/or Type B virus. 
 
Secondary Immunogenicity Objective: To evaluate the immune response after 
vaccination with QIVc, 4 weeks after last vaccination in a sub-set of subjects 6 months 
through 47 months of age in each study vaccine group. 
 
Secondary Safety Objective: To evaluate the safety and tolerability of QIVc among 
subjects 6 months through 47 months of age in the QIVc group and comparator group. 

Seqirus 
Confidential 
Protocol V130_14 
03 SEP 20 Version 3.0 
 
Page 9 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Name of Sponsor: 
Seqirus 
 
Protocol number: 
V130_14 
Generic name of study vaccine(s): 
Cell-Based Quadrivalent Subunit 
Influenza Virus Vaccine (QIVc) 
Non-Influenza Vaccine 
Study Design: 
This multicenter phase III clinical study evaluates the efficacy, immunogenicity and 
safety of a cell-based quadrivalent subunit influenza virus-vaccine compared to non-
influenza vaccine in subjects between 6 months through 47 months of age. The study 
features an observer blind design, parallel groups and 1:1 randomization between QIVc 
and a non-influenza vaccine. Based on previous influenza vaccination history, subjects 
will receive either one or two doses of either QIVc or comparator (non-influenza 
vaccine/placebo). The non-influenza vaccine is a conjugate vaccine for prevention of 
invasive disease caused by Neisseria meningitidis serogroup C (MenC vaccine). In 
subjects who require two doses, MenC and placebo (saline for injection) will be 
administered separated by 28 days. In this study placebo will be used as masking dose. 
All subjects aged 6 through 11 months at enrollment, regardless of treatment 
assignment, will receive a dose of the MenC vaccine at the end of the study.  
The study has a treatment period and a follow-up period. For subjects with a previous 
influenza vaccination history, the treatment period begins at the time of vaccination and 
ends 28 days after vaccination and will consist of 2 clinical visits and one reminder call 
to complete the subject diary card. The follow up period begins 28 days after 
vaccination and ends at the time of study completion visit. For subjects without or 
unknown previous influenza vaccination history, the treatment period begins at the time 
of first vaccination and ends 28 days after the second vaccination and will consist of 3 
clinical visits and two reminder calls to complete the subject diary card, one after each 
vaccination. The follow up period begins 28 days after second vaccination and ends at 
the time of study completion visit. All subjects, irrespective of previous influenza 
vaccination history, will receive 1 safety follow-up call 90 days after last vaccination 
during the follow up period and the follow-up period will conclude with a study 
completion visit (clinic visit or call). Safety data collection will include standard 
solicited adverse event reporting via subject diary card for 7 days after each vaccine 
administration (including the day of vaccination), all unsolicited adverse events (AEs) 
for 28 days after each vaccine administration, and special AE categories (serious 
adverse event (SAE), new onset of chronic disease (NOCD), medically-attended AEs 
for 30 days after ILI onset) for the full duration of the study. In countries, where the 

Seqirus 
Confidential 
Protocol V130_14 
03 SEP 20 Version 3.0 
 
Page 10 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Name of Sponsor: 
Seqirus 
 
Protocol number: 
V130_14 
Generic name of study vaccine(s): 
Cell-Based Quadrivalent Subunit 
Influenza Virus Vaccine (QIVc) 
Non-Influenza Vaccine 
MenC vaccine (Neisvac-C®, Pfizer) is not licensed, an extra visit will be performed only 
to assess the safety of MenC vaccine at approximately 28 days after vaccination.  
Blood samples will be collected from a sub-set of subjects participating in each 
influenza season (maximum 222 per season), during two clinic visits prior to the first 
vaccination and 28 days after last vaccination. Immunogenicity analyses will be 
performed to characterize baseline titers, response to vaccination and to understand the 
observed efficacy for the study population. 
Throughout the study, unscheduled visits are planned for subjects who manifest 
influenza-like illness (ILI) symptoms during the influenza season. The subject’s parent 
or legally acceptable representative (LAR) or delegate is contacted weekly to capture 
ILI symptoms throughout the study. When ILI symptoms occur, the 
parent/LAR/delegate should complete the ILI booklet. 
Study Duration:  
The study is designed to accrue a minimum number of influenza confirmed cases over 
several influenza seasons. Each subject will participate until the end of the influenza 
season as defined in the protocol for the season in which the subject is enrolled but at 
least 180 days after last vaccination.  
Number of Subjects planned:  
An approximate number of 3,830 subjects are planned to be enrolled and randomized 
1:1 to either QIVc (1,915 subjects) or the comparator group (1,915 subjects) taking into 
account a 10% drop-out rate. For the immunogenicity assessments, blood samples will 
be collected throughout the study up to a maximum of 222 subjects per influenza season 
(with 111 subjects in the QIVc group and 111 subjects in the comparator group). 
Study Population and Subject Characteristics:  
This study will enroll children aged 6 months through 47 months old from countries 
across the world, over several influenza seasons. The subjects should be generally 

Seqirus 
Confidential 
Protocol V130_14 
03 SEP 20 Version 3.0 
 
Page 11 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Name of Sponsor: 
Seqirus 
 
Protocol number: 
V130_14 
Generic name of study vaccine(s): 
Cell-Based Quadrivalent Subunit 
Influenza Virus Vaccine (QIVc) 
Non-Influenza Vaccine 
healthy and may have a previous history of influenza vaccination. The list of inclusion 
and exclusion criteria is included in protocol Section 4, Selection of Study Population. 
Study Procedures:  
Written informed consent must be obtained prior to any study-related procedures 
according to ICH-GCP (ICH E6 (R2)). After signing of the informed consent by the 
subject’s parent(s) or LAR and undergoing review of medical history, physical 
examination, review of current and prior medications and vaccinations, and 
confirmation of subject eligibility, subjects will be enrolled into the study.  
The study has a treatment period and a follow-up period. The treatment period has 
scheduled visits planned depending on the subject’s influenza vaccination history and 
age of the subject. The follow-up period will conclude with a study completion visit 
(clinic visit or call).  
In the exceptional case where calls or clinic visits are not feasible in some countries, 
study site personnel may visit the subject’s homes to inquire about signs and symptoms 
of illness in the subject, collect a NP swab specimen or perform other study assessments 
(see Section 5 Study Procedures) when agreed upon by the Sponsor and in line with 
country specific requirements and/or regulations. 
Treatment period:  
After vaccination, all subjects will remain under medical supervision and will be 
monitored for any immediate reactions for at least 30 minutes. The 30 minute follow-up 
data is recorded in the source documentation and the electronic data capture system 
(EDC) by the site personnel. Local adverse reactions and systemic solicited adverse 
events that occur from 30 minutes after vaccination will be collected for seven (7) days 
following each vaccination on a subject diary card. The parent/LAR or a person 
designated by the parent/LAR of all subjects will receive a reminder to complete the 
subject diary card two (2) days after vaccination. All unsolicited AEs and concomitant 
medication will be collected until 28 days after last vaccination. From a sub-set of 
subjects, a blood specimen will be collected prior to vaccination at Visit 1 and 28 days 
after last study vaccine administration at scheduled clinic visits. 

Seqirus 
Confidential 
Protocol V130_14 
03 SEP 20 Version 3.0 
 
Page 12 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Name of Sponsor: 
Seqirus 
 
Protocol number: 
V130_14 
Generic name of study vaccine(s): 
Cell-Based Quadrivalent Subunit 
Influenza Virus Vaccine (QIVc) 
Non-Influenza Vaccine 
Follow-up period:  
During the follow-up period, safety data including ‘AEs leading to withdrawal’, ‘SAEs’, 
‘NOCDs’, ‘medically-attended AEs until 30 days after ILI onset’ and all medications 
used related to these events will be captured. In case of such events, subject’s 
parent(s)/LAR will be instructed to contact the site as soon as possible to report the 
event(s). Furthermore, a safety follow-up call 90 days after last vaccination will 
performed. 
During treatment and follow-up period:  
Unscheduled visits are planned for subjects who manifest signs of influenza-like illness 
(ILI) during the influenza season and will be evaluated by testing of a nasopharyngeal 
(NP) specimen for influenza. Thirty (30) days after ILI onset, an ILI follow-up call with 
associated checklist will be performed to determine if subsequent medically-attended 
adverse events occurred including concomitant medication associated with these events.  
After enrollment, a weekly alert (for example a telephone call) will serve as a reminder 
to the subject’s parent/LAR/designate to report ILI symptoms to the study investigator. 
Subjects with ILI symptoms and its complications ought to be treated according to 
recent accepted (national) clinical standards. Subject’s parent(s)/LAR will be asked to 
contact the site immediately if health concerns arise. 
At the end of influenza season but at least 180 days after last vaccination date: 
A scheduled study visit 5 (clinic / home visit or call) at the end of influenza season but 
at least 180 days after last vaccination will occur. All subjects aged 6 through 11 months 
will receive a MenC vaccination, regardless of treatment assignment. 
In countries, where the MenC vaccine (Neisvac-C, Pfizer) is not licensed, an extra visit 
(Visit 6) is performed, only to assess the safety of the MenC vaccine at approximately 
28 days after vaccination at Visit 5. 
Study Vaccines and Schedule: 
Investigational vaccine: The investigational vaccine is Flucelvax Quadrivalent/ 
Flucelvax Tetra (QIVc, Seqirus), and contains 0.5 mL including 15 µg purified viral 

Seqirus 
Confidential 
Protocol V130_14 
03 SEP 20 Version 3.0 
 
Page 13 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Name of Sponsor: 
Seqirus 
 
Protocol number: 
V130_14 
Generic name of study vaccine(s): 
Cell-Based Quadrivalent Subunit 
Influenza Virus Vaccine (QIVc) 
Non-Influenza Vaccine 
envelope-glycoprotein hemagglutinin (HA) of each of the four (4) influenza strains 
recommended by WHO for inclusion in the quadrivalent vaccine formulation for the 
influenza season corresponding to the season of conduct of study. 
Vaccination schedule:  
• Subjects ≥ 12 months with a previous influenza vaccination history: One dose of 
QIVc at Visit 1. 
• Subjects ≥ 12 months without a previous influenza vaccination history and subjects 
6 through 11 months: One dose of QIVc at Visit 1 followed by one dose of QIVc at 
Visit 2. 
Comparator vaccine(s): Meningococcal Group C Polysaccharide Conjugate Vaccine 
(MenC vaccine, Neisvac-C, Pfizer) will be used as a comparator: 
Vaccination schedule:  
• Subjects ≥ 12 months with a previous influenza vaccination history: One dose of 
MenC vaccine at Visit 1. 
• Subjects ≥ 12 months without a previous influenza vaccination history and subjects 
6 through 11 months: One dose of MenC vaccine at Visit 1 followed by one dose of 
placebo at Visit 2. 
All subjects aged 6 through 11 months at enrollment, regardless of treatment 
assignment, will receive a dose of the MenC vaccine at Visit 5. 
Primary Efficacy Endpoint(s):  
1. a. First occurrence of RT-PCR confirmed influenza, due to any influenza Type A 
and/or B virus regardless of antigenic match to the influenza strains selected for the 
seasonal influenza vaccine, occurring at > 14 days after the last vaccination and until 
the end of the influenza season, in association with protocol-defined ILI symptoms.  
 
1. b. First occurrence of culture confirmed influenza, due to influenza Type A and/or B 
virus antigenically matched by ferret antigenicity testing to the strains selected for 
the seasonal influenza vaccine, occurring at > 14 days after the last vaccination and 

Seqirus 
Confidential 
Protocol V130_14 
03 SEP 20 Version 3.0 
 
Page 14 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Name of Sponsor: 
Seqirus 
 
Protocol number: 
V130_14 
Generic name of study vaccine(s): 
Cell-Based Quadrivalent Subunit 
Influenza Virus Vaccine (QIVc) 
Non-Influenza Vaccine 
until the end of the influenza season, in association with protocol-defined ILI 
symptoms. 
 
Secondary Efficacy Endpoint(s): 
Endpoints evaluating QIVc compared to a non-influenza vaccine: 
2. The efficacy endpoint for the objective 2 is first occurrence of culture confirmed 
influenza caused by influenza virus strains antigenically dissimilar to the influenza 
strains selected for the seasonal vaccine occurring at > 14 days after the last vaccination 
and until the end of the influenza season, in association with protocol-defined ILI 
symptoms. 
 
3. The efficacy endpoint for the objective 3 is first occurrence of culture confirmed 
influenza due to any influenza Type A and/or Type B virus regardless of antigenic 
match to the influenza strains selected for the seasonal influenza vaccine, occurring at > 
14 days after the last vaccination and until the end of the influenza season, in 
association with protocol-defined ILI symptoms. 
 
4. The efficacy endpoint for the objective 4 is first occurrence of RT-PCR confirmed 
moderate-to-severe influenza due to any influenza Type A and/or Type B virus 
regardless of antigenic match to the influenza strains selected for the seasonal influenza 
vaccine, occurring at > 14 days after the last vaccination and until the end of the 
influenza season. 
 
Secondary Immunogenicity Endpoints (immunogenicity sub-set): The measures for 
immunogenicity are determined by a haemagglutination inhibition [HI] and/or a micro 
neutralization [MN] assay prior to first vaccination and 28 days after last vaccination for 
all four influenza strains. For each assay the measures include: 
 
a) Pre and post-vaccination geometric mean titers (GMTs); 
b) Seroconversion rates (SCR): Defined as the percentage of subjects with either a 
prevaccination HI (or MN) titer < 1:10 and a postvaccination HI (or MN) titer ≥ 
1:40, or a prevaccination HI (or MN) titer ≥ 1:10 and a ≥ 4-fold increase in 
postvaccination HI (or MN) titer; 

Seqirus 
Confidential 
Protocol V130_14 
03 SEP 20 Version 3.0 
 
Page 15 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Name of Sponsor: 
Seqirus 
 
Protocol number: 
V130_14 
Generic name of study vaccine(s): 
Cell-Based Quadrivalent Subunit 
Influenza Virus Vaccine (QIVc) 
Non-Influenza Vaccine 
c) Geometric mean ratio (GMR): GMR is the geometric mean of the fold increase of 
post-vaccination HI (or MN) titer over the pre-vaccination HI (or MN) titer.  
 
Secondary Safety Endpoints: The measures for assessing safety and tolerability are as 
follows: 
1. Percentage of subjects with solicited local and systemic AEs will be assessed for 7 
days following each vaccination in the QIVc group and in the comparator group.  
2. Percentage of subjects with any unsolicited AEs will be assessed in the QIVc group 
and in the comparator group until 28 days after each vaccination. 
3. Percentage of subjects with SAEs, NOCDs, AEs leading to withdrawal from the 
study or vaccination, and all medications associated with these events will be 
reported in the QIVc group and in the comparator group. 
4. Percentage of subjects with medically-attended AEs within 30 days after ILI onset 
will be reported in the QIVc group and in the comparator group. 
Statistical Analyses:  
Statistical Considerations for Sample Size Calculations:  
This study is planned using a group sequential design, with one or more interim 
analyses for efficacy using O’Brien-Fleming accounting for a group sequential design. 
The study is designed to accrue an approximate number of subjects and a minimum 
number of cases over several influenza seasons, i.e. both a minimum of 191 RT-PCR 
confirmed influenza cases and a minimum of 104 culture confirmed influenza cases 
antigenically matched to the strains selected for the seasonal vaccine. If the 
overall/pooled influenza attack rate differs from the predicted and/or influenza strain 
circulation within a study season has drifted or shifted away from the strains selected for 
the seasonal vaccine, an adjustment of the prospectively specified number of cases, and 
number of subjects may be required. Extraneous real-life information, from (but not 
limited to) the influenza surveillance systems of the European Center for Disease 
Control (ECDC), US Center for Disease Control and Prevention (CDC) or World Health 
Organization (WHO) may be used to re-assess the influenza event rate. 
The statistical test performed will depend on the number of RT-PCR confirmed 
influenza cases and the number of culture confirmed influenza cases, so the sample size 

Seqirus 
Confidential 
Protocol V130_14 
03 SEP 20 Version 3.0 
 
Page 16 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Name of Sponsor: 
Seqirus 
 
Protocol number: 
V130_14 
Generic name of study vaccine(s): 
Cell-Based Quadrivalent Subunit 
Influenza Virus Vaccine (QIVc) 
Non-Influenza Vaccine 
estimate is only for operational reasons (an estimate of number of subjects needed to 
assess the endpoint). 
 
For the primary efficacy endpoint 1a, assuming an attack rate in the comparator group 
of 8% and an influenza vaccine efficacy (VE) of 40%, an estimated sample size of 2,974 
evaluable subjects (or 1,487 evaluable subjects per study group) with a total of 191 
cases are needed to have at least 90% power to reject the null hypothesis that the VE is 
less or equal to 0% at the significance level alpha (α) = 0.0125 and the risk of infection 
contained entirely within period covered by follow-up. For the primary efficacy 
endpoint for vaccine antigenically matched strains (1b.), assuming an attack rate in the 
comparator groups of 4%, a VE of 50%, α=0.0125, 3,446 evaluable subjects and 104 
cases are needed to have at least 90% power to reject the null hypothesis that the VE is 
less or equal to 0% at the significant level alpha (α) = 0.0125. These results assume that 
the hazard ratio is constant throughout the study and that Cox proportional hazard 
regression is used for the analysis. Accounting for 10% early dropout and uncertainty 
about the assumed parameters, 3,830 subjects are planned to be enrolled (or 1,915 
subjects per study group) to demonstrate that the lower limit (LL) of the two-sided 
97.5% CI for the VE is greater than 0% for the primary endpoint assessment. 
Primary Efficacy Analyses:  
The primary efficacy analysis will be based on the Full Analysis Set (FAS). Eligible 
subjects for FAS analysis are subjects who are randomized and received at least one 
study vaccine, and will be analyzed according to their randomized study vaccine [intent-
to-treat analysis]). Absolute vaccine efficacy will only be assessed for RT-PCR 
confirmed influenza episodes (primary efficacy objective 1a) and culture confirmed 
influenza episodes (primary efficacy objective 1b) with first onset of ILI occurring at > 
14 days after the last vaccination (since clinical protection is not immediate after 
vaccination) until the end of the influenza season. Additionally, the primary objective 
will be evaluated in Per-Protocol Analysis Set (PPAS). Additional detail is provided in 
Section 8, Statistical Considerations of the protocol and the Statistical Analysis Plan 
(SAP). 
 
Time-to-event analysis based on a proportional hazard model will be used for all 
efficacy analyses to estimate the hazard ratio (HR). Absolute vaccine efficacy (aVE) 

Seqirus 
Confidential 
Protocol V130_14 
03 SEP 20 Version 3.0 
 
Page 17 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Name of Sponsor: 
Seqirus 
 
Protocol number: 
V130_14 
Generic name of study vaccine(s): 
Cell-Based Quadrivalent Subunit 
Influenza Virus Vaccine (QIVc) 
Non-Influenza Vaccine 
against first-occurrence RT-PCR confirmed influenza cases will be defined as the 
relative reduction in influenza infection rate in the QIVc group to the comparator group, 
namely aVE = 1 – HR = 1 – [λQIVc(s)(t)/ λComp(s)(t)], where HR is the hazard ratio 
between QIVc and comparator and λ(s)(t) is the stratum-specific hazard rates of each 
study group. λ(s) (t) = f(s) (t)/S(s) (t), where f(s) (t) is the stratum-specific rate of first-
occurrence RT-PCR confirmed influenza cases per unit time t and S(s) (t) is the stratum-
specific survival function, i.e. function of time without influenza cases. The model will 
include covariates (for example age and season). The absolute efficacy will be tested 
according to the following null (H0) and alternative (H1) hypotheses: H0: 1 – HR ≤ 0 
versus H1: 1 – HR > 0. 
 
Success Criteria for the Multiple Primary Efficacy Objectives:  
The primary objective of efficacy is considered demonstrated if efficacy is demonstrated 
for at least one of the two primary efficacy endpoints, if the lower limit (LL) of the two-
sided 97.5% confidence interval (CI) of VE is greater than 0% in subjects 6 months 
through 47 months of age. 
Further details regarding the statistical methods and analyses will be further specified in 
the statistical Section 8, Statistical Consideration of the protocol and the Statistical 
Analysis Plan (SAP). 
Interim Analysis:  
An event-driven interim analysis may be performed if deemed necessary by the 
Sponsor. In the event an interim is performed, the goal of the interim analysis is to be 
able to stop the study for early evidence of efficacy. For this analysis a restricted 
unblinding will be done, i.e. only external DMC members and Contract Research 
Organization (CRO) employees executing the unblinding receive access to the 
randomization codes and unblinded data for the purpose of preparing the interim 
analyses. Interim analyses are only intended to determine if the trial has met criteria for 
efficacy. Further details regarding the interim analysis are contained in Section 8.6, 
Interim Analysis. 

Seqirus 
Confidential 
Protocol V130_14 
03 SEP 20 Version 3.0 
 
Page 18 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Name of Sponsor: 
Seqirus 
 
Protocol number: 
V130_14 
Generic name of study vaccine(s): 
Cell-Based Quadrivalent Subunit 
Influenza Virus Vaccine (QIVc) 
Non-Influenza Vaccine 
Data Monitoring Committee:  
An independent DMC will be utilized for the study for the evaluation of safety during 
the study and efficacy data for interim analysis. The DMC may recommend to stop the 
study for efficacy when at least one efficacy objective met the success criteria described 
in the Statistical Analysis Plan or if a safety concern is identified, otherwise the trial will 
continue as planned. There are no futility criteria at the interim analysis. Additional 
details regarding the review of the data by the DMC will be contained in the DMC 
Charter and Section 3.7, Data Monitoring Committee. 
 

Seqirus 
                                                                       Confidential 
 
 
 
         Protocol V130_14 
03 SEP 20 Version 3.0 
 
 
 
 
 
Page 19 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Table 1.1 
Time and Events Table – Treatment and Follow-up Period for subjects without or unknown previous 
influenza vaccination history (two dose regimen) 
 
 
Treatment Period 
Follow-up Periodb,c 
 
Visit Type 
Clinic Visita 
Diary 
Reminder 
Calla 
Clinic Visita 
Diary 
Reminder 
Calla 
Clinic Visita 
Safety 
Follow-up 
Calla 
Clinic Visita 
 
Study Day 
 
V1 + 2d 
V1 + 28 
V2 + 2c 
V2 + 28 
V2 + 90 
End of 
influenza 
season or 
180 days 
after last 
vaccinatione
,* 
V5 + 28 
 
Visit Number 
V1 
 
V2 
 
V3 
V4 
V5 
V6c 
 
Visit Window 
(Days) 
n/a 
-1/+1 
 0 to +7 
-1/+1 
0 to +7 
0 to +7 
0 to +14 
0 to +7 
Study Event 
References 
 
 
 
 
 
 
 
 
Screening and Safety 
Informed Consentf 
Section 5.1.1 
√f 
 
 
 
 
 
 
 
Review of Systemsg 
Section 5.1.2 
√g 
 
 
 
 
 
 
 
Medical Historyg 
Section 5.1.2 
√g 
 
 
 
 
 
 
 
Demographic Informationg 
Section 5.1.2 
√g 
 
 
 
 
 
 
 
Physical Examinationg 
Sections 5.1.2 
and 5.3.1 
√g 
 
√g 
 
√ 
 
√ 
 
Exclusion/Inclusion Criteriag 
Section 4 
√g 
 
√g 
 
 
 
 
 

Seqirus 
                                                                       Confidential 
 
 
 
         Protocol V130_14 
03 SEP 20 Version 3.0 
 
 
 
 
 
Page 20 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
 
 
Treatment Period 
Follow-up Periodb,c 
 
Visit Type 
Clinic Visita 
Diary 
Reminder 
Calla 
Clinic Visita 
Diary 
Reminder 
Calla 
Clinic Visita 
Safety 
Follow-up 
Calla 
Clinic Visita 
 
Study Day 
 
V1 + 2d 
V1 + 28 
V2 + 2c 
V2 + 28 
V2 + 90 
End of 
influenza 
season or 
180 days 
after last 
vaccinatione
,* 
V5 + 28 
 
Visit Number 
V1 
 
V2 
 
V3 
V4 
V5 
V6c 
 
Visit Window 
(Days) 
n/a 
-1/+1 
 0 to +7 
-1/+1 
0 to +7 
0 to +7 
0 to +14 
0 to +7 
Study Event 
References 
 
 
 
 
 
 
 
 
Influenza and MenC 
Vaccination Historyg 
Section 5.1.2 
√g 
 
 
 
 
 
√g 
 
Randomizationg 
Section 5.1.4 
√g 
 
 
 
 
 
 
 
Subject Diary Card Training 
Section 5.2.1 
√ 
 
√ 
 
 
 
 
 
Subject Diary Card Reminder 
Section 5.2.2 
 
√ 
 
√ 
 
 
 
 
Subject Diary Card Review 
and Collection 
Section 5.3.1 
 
 
√g 
 
√ 
 
 
 
Assess all AEsg 
Section 7.1 
√g 
 
√g 
 
√ 
 
 
 
Collection of information on 
SAEs 
Section 7.1.4 
At any time during the study period 
Assess AEs Leading to 
Withdrawal, NOCDs 
Sections 7.2 and 
7.1.3 
 
 
 
 
 
√ 
√ 
√ 

Seqirus 
                                                                       Confidential 
 
 
 
         Protocol V130_14 
03 SEP 20 Version 3.0 
 
 
 
 
 
Page 21 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
 
 
Treatment Period 
Follow-up Periodb,c 
 
Visit Type 
Clinic Visita 
Diary 
Reminder 
Calla 
Clinic Visita 
Diary 
Reminder 
Calla 
Clinic Visita 
Safety 
Follow-up 
Calla 
Clinic Visita 
 
Study Day 
 
V1 + 2d 
V1 + 28 
V2 + 2c 
V2 + 28 
V2 + 90 
End of 
influenza 
season or 
180 days 
after last 
vaccinatione
,* 
V5 + 28 
 
Visit Number 
V1 
 
V2 
 
V3 
V4 
V5 
V6c 
 
Visit Window 
(Days) 
n/a 
-1/+1 
 0 to +7 
-1/+1 
0 to +7 
0 to +7 
0 to +14 
0 to +7 
Study Event 
References 
 
 
 
 
 
 
 
 
Collect Relevant Medications 
and Vaccinations 
Sections 5.1.2 
and 6.5 
At any time during the study period 
Immunogenicity 
Serology Blood Drawg,h 
Section 3.5 
√g,h 
 
 
 
√h 
 
 
 
Collect Relevant Medications 
and Vaccinations 
Sections 5.1.2 
and 6.5 
At any time during the study period 
Study Treatment 
Vaccination  
Section 5.2 
√ 
 
√ 
 
 
 
 
 
30 Minutes Post Injection 
Assessment 
Section 5.2.1 
√ 
 
√ 
 
 
 
 
 
Efficacy 

Seqirus 
                                                                       Confidential 
 
 
 
         Protocol V130_14 
03 SEP 20 Version 3.0 
 
 
 
 
 
Page 22 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
 
 
Treatment Period 
Follow-up Periodb,c 
 
Visit Type 
Clinic Visita 
Diary 
Reminder 
Calla 
Clinic Visita 
Diary 
Reminder 
Calla 
Clinic Visita 
Safety 
Follow-up 
Calla 
Clinic Visita 
 
Study Day 
 
V1 + 2d 
V1 + 28 
V2 + 2c 
V2 + 28 
V2 + 90 
End of 
influenza 
season or 
180 days 
after last 
vaccinatione
,* 
V5 + 28 
 
Visit Number 
V1 
 
V2 
 
V3 
V4 
V5 
V6c 
 
Visit Window 
(Days) 
n/a 
-1/+1 
 0 to +7 
-1/+1 
0 to +7 
0 to +7 
0 to +14 
0 to +7 
Study Event 
References 
 
 
 
 
 
 
 
 
ILI Symptom Assessment 
and Documentation Trainingi 
Section 5.2.5 
√i 
 
 
 
 
 
 
 
ILI Reminder Callsj 
Section 5.4.1 
√j 
 
Study Completion Procedures 
Procedures 
Section 5.5 
 
 
 
 
 
 
√ 
 
 Vaccinationk 
Section 5.5 and 
6.2  
 
 
 
 
 
 
√k 
 
30 Minutes Post Injection 
Assessmentk 
Section 5.2.1 
 
 
 
 
 
 
√k 
 

Seqirus 
                                                                       Confidential 
 
 
 
         Protocol V130_14 
03 SEP 20 Version 3.0 
 
 
 
 
 
Page 23 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
a) In the exceptional case where calls or clinic visits are not feasible in some countries, study site personnel may visit the subject’s homes to inquire about signs and symptoms 
of illness in the subject, collect a NP swab specimen or perform other study assessments (see Section 5 Study Procedures), when agreed upon by the Sponsor and in line with 
country specific requirements and/or regulations. 
b) Visit 5 is a call for subjects aged 12 months and older at enrollment, and is a clinic visit for subjects 6 through 11 months at enrollment 
c) Study completion is at visit 6 ONLY for subjects aged 6 through 11 months at enrollment, who are enrolled in a country WITHOUT a NeisVac-C (MenC) vaccine marketing 
authorization. Visit 6 can be call. For all other subjects’ study completion is at visit 5; visit 6 is not required.  
d) A subject diary reminder call is a call approximately 2 days after vaccination 
e) Performed at End of Influenza Season but at least 180 days after last vaccination date 
f) 
Informed Consent Form can be collected before Study day 1 
g) Procedures that should be completed before vaccination 
h) Blood draws are only applicable for subjects randomized into the immunogenicity sub-set. Collect blood samples before vaccination   
i) 
ILI Symptom Assessment and Documentation Training includes use of ILI Booklet to be completed if an ILI occurs 
j) 
Performed until End of Influenza Season 
k) Subjects aged 6 through 11 months at enrollment will receive a dose of the MenC vaccine at study completion visit.  
*Should an ILI be identified and a NP swab obtained, it is recommended to postpone the study completion visit, to allow for the ILI follow-up visit to occur (see Section 5.5, 
Study Completion) 

Seqirus 
                                                                       Confidential 
 
 
 
         Protocol V130_14 
03 SEP 20 Version 3.0 
 
 
 
 
 
Page 24 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Table 1.2 
Time and Events Table – Treatment and Follow-up Period for subjects with a previous influenza 
vaccination history (one dose regimen) 
 
 
Treatment Period 
Follow-up Period 
 
Visit Type 
Clinic 
Visita 
Diary 
Reminder 
Calla 
Clinic 
Visita 
Safety Follow-up Calla 
Clinic Visita,b,* 
 
Study Day 
1 
V1 + 2c 
V1 + 28 
V1 + 90 
End of influenza season or 180 
days after last vaccinationd 
 
Visit Number 
V1 
 
V2 
V3 
V4 
 
Visit Window 
(Days) 
n/a 
-1/+1 
 0 to +7 
0 to +7 
0 to +14 
Study Event 
References 
 
 
 
 
 
Screening and Safety 
Informed Consente 
Section 5.1.1 
√e 
 
 
 
 
Review of Systemsf 
Section 5.1.2 
√f 
 
 
 
 
Medical Historyf 
Section 5.1.2 
√f 
 
 
 
 
Demographic Informationf 
Section 5.1.2 
√f 
 
 
 
 
Physical Examinationf 
Sections 5.1.2 
and 5.3.1 
√f 
 
√f 
 
 
Exclusion/Inclusion Criteriaf 
Section 4 
√f 
 
 
 
 
Influenza and MenC Vaccination 
Historyf 
Section 5.1.2 
√f 
 
 
 
√f 
Randomizationf 
Section 5.1.4 
√f 
 
 
 
 
Subject Diary Card Training 
Section 5.2.1 
√ 
 
 
 
 
Subject Diary Card Reminder 
Section 5.2.2 
 
√ 
 
 
 

Seqirus 
                                                                       Confidential 
 
 
 
         Protocol V130_14 
03 SEP 20 Version 3.0 
 
 
 
 
 
Page 25 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
 
 
Treatment Period 
Follow-up Period 
 
Visit Type 
Clinic 
Visita 
Diary 
Reminder 
Calla 
Clinic 
Visita 
Safety Follow-up Calla 
Clinic Visita,b,* 
 
Study Day 
1 
V1 + 2c 
V1 + 28 
V1 + 90 
End of influenza season or 180 
days after last vaccinationd 
 
Visit Number 
V1 
 
V2 
V3 
V4 
 
Visit Window 
(Days) 
n/a 
-1/+1 
 0 to +7 
0 to +7 
0 to +14 
Study Event 
References 
 
 
 
 
 
Subject Diary Card Review and 
Collection 
Section 5.3.1 
 
 
√f 
 
 
Assess all AEsf 
Section 7.1 
√f 
 
√f 
 
 
Collection of information on SAEs 
Section 7.1.4 
At any time during the study period 
Assess AEs Leading to 
Withdrawal, NOCDs 
Sections 7.2  and 
7.1.3 
 
 
 
√ 
√ 
Collect Relevant Medications and 
Vaccinations 
Sections 5.1.2 
and 6.5 
At any time during the study period 
Immunogenicity 
Serology Blood Drawf,g 
Section 3.5 
√f,g 
 
√g 
 
 
Study Treatment 
Vaccination  
Section 5.2 
√ 
 
 
 
 
30 Minutes Post Injection 
Assessment 
Section 5.2.1 
√ 
 
 
 
 
Efficacy 

Seqirus 
                                                                       Confidential 
 
 
 
         Protocol V130_14 
03 SEP 20 Version 3.0 
 
 
 
 
 
Page 26 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
 
 
Treatment Period 
Follow-up Period 
 
Visit Type 
Clinic 
Visita 
Diary 
Reminder 
Calla 
Clinic 
Visita 
Safety Follow-up Calla 
Clinic Visita,b,* 
 
Study Day 
1 
V1 + 2c 
V1 + 28 
V1 + 90 
End of influenza season or 180 
days after last vaccinationd 
 
Visit Number 
V1 
 
V2 
V3 
V4 
 
Visit Window 
(Days) 
n/a 
-1/+1 
 0 to +7 
0 to +7 
0 to +14 
Study Event 
References 
 
 
 
 
 
ILI Symptom Assessment and 
Documentation Trainingh 
Section 5.2.5 
√h 
 
 
 
 
ILI Reminder Callsi 
Section 5.4.1 
√i 
Study Completion Procedures 
Study Completion 
Section 5.5 
 
 
 
 
√ 

Seqirus 
                                                                       Confidential 
 
 
 
         Protocol V130_14 
03 SEP 20 Version 3.0 
 
 
 
 
 
Page 27 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
 
 
Treatment Period 
Follow-up Period 
 
Visit Type 
Clinic 
Visita 
Diary 
Reminder 
Calla 
Clinic 
Visita 
Safety Follow-up Calla 
Clinic Visita,b,* 
 
Study Day 
1 
V1 + 2c 
V1 + 28 
V1 + 90 
End of influenza season or 180 
days after last vaccinationd 
 
Visit Number 
V1 
 
V2 
V3 
V4 
 
Visit Window 
(Days) 
n/a 
-1/+1 
 0 to +7 
0 to +7 
0 to +14 
Study Event 
References 
 
 
 
 
 
a) In the exceptional case where calls or clinic visits are not feasible in some countries, study site personnel may visit the subject’s homes to inquire about signs and symptoms 
of illness in the subject, collect a NP swab specimen or perform other study assessments (see Section 5 Study Procedures), when agreed upon by the Sponsor and in line with 
country specific requirements and/or regulations. 
b) Study completion visit is a call for subjects aged 12 months and older at enrollment, and is a clinic visit for subjects 6 through 11 months at enrollment 
c) A subject diary reminder call is a call approximately 2 days after vaccination 
d) Performed at End of Influenza Season but at least 180 days after last vaccination 
e) Informed Consent Form can be collected before Study day 1 
f) 
Procedures that should be completed before vaccination 
g) Blood draws are only applicable for subjects randomized into the immunogenicity sub-set. Collect blood samples before vaccination 
h) ILI Symptom Assessment and Documentation Training includes use of ILI Booklet to be completed if an ILI occurs 
i) 
Performed until End of Influenza Season 
*Should an ILI be identified and a NP swab obtained, it is recommended to postpone the study completion visit, to allow for the ILI follow-up visit to occur (see Section 5.5, 
Study Completion) 
 

Seqirus 
                                                                       Confidential 
 
 
 
         Protocol V130_14 
03 SEP 20 Version 3.0 
 
 
 
 
 
Page 28 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Table 1.3 
Time and Events Table – Unscheduled visit(s) related to a protocol defined ILI episodea 
 
Visit Type 
Unscheduled Clinic Visitb 
ILI Follow-up Callc,* 
 
ILI Onset Day 
1d 
+ 30 
 
Visit Number 
n/a 
n/a 
 
Visit Window 
(Days) 
0 to +6 
0 to +7 
Study Event 
References 
 
 
 
 
 
Efficacy 
ILI Booklet Review and 
Collection 
Section 5.4.2 
√ 
 
Assess ILI symptoms 
Sections 5.4.3 
and 7.2 
√ 
√ 
ILI Nasopharyngeal Swab 
Collectiond 
Sections 3.5 and 
5.4.2 
√d 
 
Assess Relevant Medications 
and Vaccinations 
Sections 5.1.2, 
5.4.3 and 6.5 
√ 
√ 
Assess Medically-Attended 
AEse 
Sections 5.4.3 
and 7.1.2 
√e 
√e 
Physical Examination 
Sections 5.1.2 
and 5.3.1 
√ 
 
ILI Symptom Assessment 
and Documentation Trainingf 
Section 5.2.5 
√f 
 

Seqirus 
                                                                       Confidential 
 
 
 
         Protocol V130_14 
03 SEP 20 Version 3.0 
 
 
 
 
 
Page 29 of 115 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
 
Visit Type 
Unscheduled Clinic Visitb 
ILI Follow-up Callc,* 
 
ILI Onset Day 
1d 
+ 30 
 
Visit Number 
n/a 
n/a 
 
Visit Window 
(Days) 
0 to +6 
0 to +7 
Study Event 
References 
 
 
 
 
 
a) Influenza-like illness (ILI) is defined by the presence of a temperature ≥ 37.8°C (≥ 100.0°F) and at least one of the following symptoms on the same day: cough, sore throat, 
nasal congestion, rhinorrhea, earache or ear discharge 
b) In the exceptional case that the subject cannot visit the study center, a home visit can be made 
c) In countries, in the exceptional case where calls are not feasible, study site personnel may visit the subject’s homes to inquire about signs and symptoms of illness in the 
subject. 
d) Subject will be asked to come to the study site within the first 24 hours or as soon as possible following ILI onset to ensure optimal viral yield 
e) A “medically-attended adverse event” is an adverse event requiring hospitalization, or emergency room visit, or visit to/by a health care provider. See section Definitions.  
f) 
ILI Symptom Assessment and Documentation Training includes use of ILI Booklet to be completed if an ILI occurs 
*Should an ILI be identified and a NP swab obtained, it is recommended to postpone the study completion visit, to allow for the ILI follow-up visit to occur (see Section 5.5, 
Study Completion) 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 30 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
LIST OF ABBREVIATIONS 
AE  
 
Adverse Event 
BLA   
Biologics License Application 
CBER   
Center for Biologics Evaluation and Research 
CDC   
Centers for Disease Control and Prevention 
CHMP  
Committee for Medicinal Products for Human Use 
CI  
 
Confidence Interval 
CRF   
Case Report Form 
CRO   
Contract Research Organization 
CSR   
Clinical Study Report 
DMC   
Data Monitoring Committee 
EC  
 
Ethics Committee 
eCRF   
Electronic Case Report Form 
EDC   
Electronic Data Capture 
EMA   
European Medicines Agency 
FAS   
Full Analysis Set 
FDA   
Food and Drug Administration 
GCP   
Good Clinical Practices 
GMR   
Geometric Mean Ratio 
GMT   
Geometric Mean Titer 
HA  
 
Hemagglutinin 
HI  
 
Haemagglutination Inhibition 
HIPAA  
Health Insurance Portability and Accountability Act 
HR 
 
Hazard ratio 
IA 
 
Interim Analysis 
IB  
 
Investigator’s Brochure 
ID  
 
Identification 
ICF  
 
Informed Consent Form 
ICH   
International Conference on Harmonisation 
ICU 
 
Intensive Care Unit 
ILI  
 
Influenza-Like Illness 
IM  
 
Intramuscular 
IRB  
 
Institutional Review Board 
IRT  
 
Interactive Response Technology 
LAR  
Legally Acceptable Representative(s) 
LL 
 
Lower Limit 
MDCK cells Madin Darby Canine Kidney cells 
MedDRA  
Medical Dictionary for Regulatory Activities 
MenC  
Meningococcal (Group C) Conjugate Vaccine 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 31 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
MN  
 
Microneutralization 
NA  
 
Neuraminidase 
NP  
 
Nasopharyngeal 
NH  
 
Northern Hemisphere 
NOCD  
New Onset of Chronic Disease 
PCR   
Polymerase Chain Reaction 
PDCO  
Paediatric Committee 
PFS  
 
Pre-filled syringes 
PIP 
 
Paediatric Investigation Plan 
PP  
 
Per Protocol 
PPAS   
Per Protocol Analysis Set 
PRO   
Patient Reported Outcome 
PV  
 
Pharmacovigilance 
QIVc   
Cell-derived Quadrivalent Influenza Vaccine 
QIV   
Quadrivalent Influenza Vaccine 
Qs 
 
Quantity sufficient 
RT-PCR  
Reverse Transcription Polymerase Chain Reaction 
SAE   
Serious Adverse Event 
SAP   
Statistical Analysis Plan 
sBLA   
Supplement Biologics License Application 
SC  
 
Seroconversion 
SDA   
Source Data Agreement 
SH  
 
Southern Hemisphere 
SOP   
Standard Operating Procedure 
SPC 
 
Summary of Product Characteristics 
TIV  
 
Trivalent Influenza Vaccine 
USPI  
United States Patient Information leaflet 
VE 
 
Vaccine Efficacy 
WHO   
World Health Organization 
 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 32 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
LIST OF DEFINITIONS 
Active ILI surveillance: Is from first vaccination through end of the influenza season. 
Antigenic match is defined as antigenic similarity to a strain contained in the influenza 
vaccine. The influenza strain responsible for a confirmed influenza case is considered as 
antigenically similar to an influenza strain contained in the influenza vaccine if the ferret 
antigenicity testing (using hemagglutination inhibition or microneutralization method 
against a panel of known standard ferret reference antisera to different viral strains) shows 
that the virus detected is similar to any of those contained in the influenza vaccine 
formulation for the respective season.  
Any Type A and/or Type B virus: Defined as any influenza virus strains included in the 
influenza vaccine, i.e. Type A (A/H1N1, A/H3N2) and/or Type B. 
Clinic visit: A clinic visit can be a home visit, clinic visit (at study site) or call. 
Culture confirmed influenza case: A case of protocol defined ILI for which a swab 
specimen yields influenza Type A and/or Type B virus by viral culture analysis.  
End of influenza season: Defined as the end of May for Northern Hemisphere (NH) 
influenza season and end of November for Southern Hemisphere (SH) influenza season. 
For tropical countries, with no typical NH or SH influenza season, the season is defined 
by the use of the strains in the influenza vaccine formulation (i.e. strains as recommended 
for the NH or the SH influenza season). Investigators will receive a notification of end of 
season. 
Follow-up period: The follow-up period starts for subjects 28 days after last vaccination 
and continues for up to study completion visit, defined as end of influenza season but at 
least 180 days after last vaccination date. 
Influenza-like illness (ILI) is defined by the presence of a temperature ≥ 37.8°C (≥ 
100.0°F) and at least one of the following symptoms on the same day: cough, sore throat, 
nasal congestion, rhinorrhea, earache or ear discharge. Definitive diagnosis of influenza 
“illness” requires laboratory confirmation of influenza virus. 
Influenza-like illness (ILI) onset is defined as the first day that a subject meets the 
criteria for protocol defined ILI.  
Influenza-like illness (ILI) resolution is defined as the first day when the following 
conditions are met simultaneously: temperature < 37.5°C (< 99.5°F) with no fever 
reducers used, other symptoms (cough, sore throat, nasal congestion, rhinorrhea, earache 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 33 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
or ear discharge) either absent or mild, and a return of the child to normal activities 
(Jacobs, 2000) (Shepperd, 2004). 
Influenza confirmed case: RT-PCR confirmed influenza in a subject who meets the 
criteria for protocol defined ILI. 
Legally Acceptable Representative(s): An individual or juridical or other body 
authorized under applicable law to consent, on behalf of a prospective subject, to the 
subject's participation in the clinical trial (see ICH-GCP, ICH E6 (R2)). 
Lower respiratory tract illness: Defined as either shortness of breath, pulmonary 
congestion, pneumonia, bronchiolitis, bronchitis, wheezing, or croup. 
Medically attended visit: Defined as a hospitalization, emergency room/ department visit 
or a visit to/ by a healthcare provider for symptoms or illnesses. Scheduled clinic study 
visits and unscheduled study visits related to protocol defined ILI are not part of this 
definition. 
Qualified healthcare professional: Any licensed health care professional who is 
permitted by institutional policy to perform clinical interventions and assessments such as 
physical examinations, is trained on the study procedure(s) and who is identified within 
the site signature and delegation log. 
Moderate-to-severe ILI episode: ILI episode complicated by one of the following: 
physician confirmed lower respiratory tract illness, physician confirmed acute otitis 
media, or hospitalization in the Intensive Care Unit (ICU), physician-diagnosed serious 
extra-pulmonary complication of influenza or supplemental oxygen requirement for more 
than 8 hours. 
New onset of ILI episode: As a guidance, another episode and swab sample should only 
be collected when the interval between the onset of protocol defined ILI to the next onset 
of protocol defined ILI is 14 days or more. 
Not-previously influenza vaccinated subject: A subject that has not received 2 or more 
doses of influenza vaccine prior to the current influenza season, or who does not know the 
influenza vaccination history. 
Previously influenza vaccinated subject: A subject with a known history of at least 2 
influenza doses prior to the current influenza season. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 34 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
RT-PCR confirmed influenza case: A case of protocol defined ILI for which a swab 
specimen yields influenza Type A and/or Type B virus by reverse transcription-
polymerase chain reaction (RT-PCR). 
Serious extra-pulmonary complications of influenza are defined as complications 
including myositis, encephalitis or other neurologic condition including seizure, 
myocarditis / pericarditis or other serious medical condition. 
Solicited adverse events are either solicited local adverse reactions or solicited systemic 
adverse events. 
Trained healthcare professional: Any health care professional who is permitted by 
institutional policy, trained to perform delegated tasks, is trained on the study 
procedure(s) and who is identified within the site signature and delegation log. 
Treatment period: Per protocol treatment period begins at the time of vaccination and 
ends 28 days after last vaccination, which is visit 2 for previously influenza vaccinated 
subjects and at visit 3 for not-previously influenza vaccinated subjects.

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 35 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
1. 
BACKGROUND AND RATIONALE 
1.1 
Background 
Influenza is an infectious disease caused by the influenza virus, an orthomyxovirus with 
two clinically relevant types (Type A and B). The disease is characterized by the abrupt 
onset of respiratory and systemic symptoms, such as fever, cough, sore throat and rhinitis. 
It occurs in epidemics throughout the northern and southern hemisphere winter months in 
temperate climates. Influenza Type A/H1N1, A/H3N2, and Type B/Victoria and 
B/Yamagata strains have circulated and caused disease in humans on a global basis since 
1977 (Fiore, 2010), with a high susceptibility to severe influenza in children (Izurieta, 
2000) (Bourgeois, 2006). Children aged < 5 years, and particularly those < 2 years of age, 
are at high risk of infection and are a priority for annual seasonal influenza vaccination 
throughout the world (WHO, 2012) (AAP, 2016). With vaccination as the recommended 
method to prevent influenza, both childhood influenza disease burden and community 
viral transmission could be reduced (Mertz, 2016). 
One of the challenges of protecting children against influenza is providing an influenza 
vaccine with an antigenic match against the circulating strains in a given influenza 
season. Since 1983, two evolutionarily distinct lineages of influenza B viruses have co-
circulated in the human population globally and influenza B viruses account for roughly 
20% of total influenza cases in all regions of the world (Caini, 2015). As only one B 
lineage is selected for inclusion in current trivalent influenza vaccines and in the absence 
of proven cross protection between the two lineages (Peltola, 2003) (Hu, 2004), there is 
the risk of a mismatch for the influenza B strain (Couch, 2007) (Belshe, 2010) (Orsi, 
2018). Since patients infected with influenza B are usually younger than patients infected 
with influenza A, the effectiveness of vaccination in children seems more dependent on 
adequate matching (Jayasundara, 2014) (Caini, 2015) (Orsi, 2018). Furthermore, at such 
young age children have not been exposed greatly to circulating influenza viruses and 
immune priming by (repeated exposure to) vaccination cannot protect them against 
disease (Quiñones-Parra, 2016).  
 
To address this challenge, quadrivalent influenza vaccines (QIV) have been developed 
containing B strains from both lineages. Although results show benefits of QIV 
vaccination in adults, results from randomized controlled trials in children immunized 
with QIV, are scarce (Jefferson, 2012) (Jain, 2013) (Claeys, 2018) (Pepin, 2017). 
Furthermore, limited data from randomized trials on the efficacy of inactivated trivalent 
influenza vaccines in children < 6 years are available and results are inconsistent 
(Jefferson, 2012) possibly explained by mild influenza virus activity, short study duration 
and suboptimal vaccine-match during the studies (Hoberman, 2003) (Jansen, 2008) 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 36 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
(Dewe, 2013) (Rolfes, 2017) including insufficient power to show effects in young 
children (Li-Kim-Moy, 2017). 
 
A second challenge is designing a study that captures the clinically relevant outcomes of 
influenza rather than mild upper respiratory tract illness. Parents are most likely to seek 
medical help for children who have symptoms of lower respiratory tract disease, high 
temperature or earache (Saunders, 2003). Studies that do not differentiate these 
manifestations of influenza from mild illness cannot assess the effectiveness of the 
influenza vaccine in attenuating illness and therefore may undervalue its benefit (Jain, 
2013) (Ambrose, 2014).  
 
Seqirus’ quadrivalent (QIVc) Flucelvax Quadrivalent / Flucelvax Tetra, is a cell based 
quadrivalent inactivated subunit influenza vaccine prepared from virus propagated in 
Madin Darby Canine Kidney (MDCK) cells, and approved by the FDA for use in children 
aged 4 years and older. A shift from eggs to cell culture has several advantages, for 
example it avoids the risk of egg-adaptive mutations in the HA protein and providing 
better manufacturing control through a closed-system fermentation process (Lambert, 
2010). As a quadrivalent vaccine, QIVc is formulated to contain two influenza A strains 
and two influenza B strains updated annually as recommended by the World Health 
Organization (WHO) for a specific influenza season, thereby increasing the adequate 
match to circulating influenza strains. 
1.2  
Potential Risks and Benefits 
There are risks associated with study participation and vaccination. These risks include 
those associated with the investigational (QIVc) or the comparator vaccine 
(meningococcal group C vaccine), the vaccination procedure, blood collection (if 
applicable), and NP swab(s) collection (if applicable). The Investigator´s Brochures 
‘Trivalent Influenza Vaccine (TIVc) and Quadrivalent Influenza Vaccine(QIVc)’, section 
‘Effects in Humans’ provides an overview of all the clinical data on QIVc. 
Meningococcal conjugate group C vaccines are routinely used in infant and toddlers’ 
immunization schedules in many European countries and globally since 1999. The MenC 
vaccine will be given according to the indications and dosing regimen described in the 
Summary of Product Characteristics (SPC). The potential risks are described and 
available in the SPC.  
Seqirus’ quadrivalent influenza vaccine is approved by the FDA for use in children aged 
4 years and older and this study is to confirm the clinical benefit of QIVc in children 6 
through 47 months of age. Therefore, the Investigator’s Brochure should be reviewed 
prior to study start. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 37 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
1.3 
Rationale 
The aim of this Phase III randomized clinical study is to evaluate the absolute vaccine 
efficacy of QIVc in the prevention of RT-PCR confirmed influenza Type A and/or Type 
B disease in children 6 through 47 months of age, compared to a non-influenza vaccine, 
using conventional endpoints and an additional endpoint that captures clinically relevant 
outcomes of influenza, associated with influenza-like illness. To overcome risks 
associated seasonal variations in influenza virus circulation, the study will continue for 
several seasons. By successfully demonstrating that QIVc decreases influenza disease in 
this age group, it will have the potential to play an important role in the prevention of 
influenza worldwide. 
The study is part of a paediatric investigation plan (PIP) agreed by the European 
Medicines Agency's (EMA) Paediatric Committee (PDCO) to support the authorization of 
QIVc in children ≥ 6 months of age. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 38 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
2. 
OBJECTIVES 
In this study, efficacy will be evaluated in all subjects in association with first occurrence of 
influenza-like illness (ILI) symptoms occurring > 14 days after last vaccination and until the 
end of the influenza season in subjects 6 months through 47 months of age at enrollment. 
Influenza-like illness (ILI) is defined by the presence of a temperature ≥ 37.8°C (≥ 100.0°F) 
and at least one of the following symptoms on the same day: cough, sore throat, nasal 
congestion, rhinorrhea, earache or ear discharge. 
2.1 
Primary Objective(s) 
Primary Efficacy Objective(s) 
1) To demonstrate the absolute vaccine efficacy of QIVc versus a comparator to prevent at 
least one of the following:  
a) RT-PCR confirmed illness caused by any influenza Type A and/or Type B virus, 
regardless of antigenic match.  
b) Culture confirmed illness caused by influenza virus strains antigenically matched to the 
influenza strains selected for the seasonal influenza vaccine. 
2.2 
Secondary Objective(s) 
Secondary Efficacy Objective(s) 
Objectives evaluating QIVc compared to a non-influenza vaccine: 
2) Prevention of culture confirmed illness caused by influenza virus strains antigenically 
dissimilar to the influenza strains selected for the seasonal vaccine. 
3) Prevention of culture confirmed illness caused by any Type A and/or Type B virus.  
4) Prevention of RT-PCR confirmed moderate-to-severe illness caused by any influenza 
Type A and/or Type B virus. 
Secondary Immunogenicity Objective(s) 
5) To evaluate the immune response after vaccination with QIVc, 4 weeks after last 
vaccination in a sub-set of subjects 6 months through 47 months of age in each study 
vaccine group. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 39 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Secondary Safety Objective(s) 
6) To evaluate the safety and tolerability of QIVc among subjects 6 months through 47 
months of age in each study vaccine group. 
2.3 
Exploratory Objective(s) 
Exploratory objectives: 
1) 
To characterize the immune response by other assays. 
2) 
To use genotypic methods to characterize circulating strains of influenza collected 
during the study. 
For exploratory endpoints refer to Section 8.1.3, Exploratory Endpoint(s).  

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 40 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
3. 
STUDY DESIGN 
3.1 
Overview of Study Design 
This multicenter phase III clinical study evaluates the efficacy, safety and 
immunogenicity of a cell-based quadrivalent subunit influenza virus-vaccine (QIVc) 
compared to non-influenza vaccine in subjects between 6 months through 47 months of 
age. The study features an observer blind design, parallel groups and 1:1 randomization 
between QIVc and the non-influenza vaccine. Based on previous influenza vaccination 
history, subjects will receive either one or two doses of either QIVc or comparator (non-
influenza vaccine/placebo). The non-influenza vaccine is a conjugate vaccine for 
prevention of invasive disease caused by Neisseria meningitidis serogroup C (MenC 
vaccine). In subjects who require two doses, MenC and placebo (saline for injection) will 
be administered separated by 28 days. In this study placebo will be used as masking dose. 
All subjects aged 6 through 11 months at enrollment, regardless of treatment assignment, 
will receive a dose of the MenC vaccine at the end of the study. For the subjects allocated 
to the immunogenicity sub-set, blood samples will be collected during clinical visits to 
allow immunogenicity analyses to further characterize the study population for baseline 
titers, response to vaccination and to understand the observed efficacy. An Interactive 
Response Technology (IRT) system will be used for subject randomization into the 
treatment group and into the immunogenicity sub-set. 
The study is designed to accrue an approximate number of subjects and a minimum 
number of cases over several influenza seasons, i.e. both a minimum of 191 RT-PCR 
confirmed influenza cases and a minimum of 104 culture confirmed influenza cases 
antigenically matched to the strains selected for the seasonal vaccine. If the overall/pooled 
influenza attack rate differs from the predicted and/or influenza strain circulation within a 
study season has drifted or shifted away from the strains selected for the seasonal vaccine, 
an adjustment of the prospectively specified number of cases, and number of subjects 
may be required. Extraneous real-life information, from (but not limited to) the influenza 
surveillance systems of the European Center for Disease Control (ECDC), US Center for 
Disease Control and Prevention (CDC) or World Health Organization (WHO) may be 
used to re-assess the influenza event rate. 
Throughout the study, unscheduled visits are planned for subjects who manifest signs of 
influenza-like illness (ILI) during the influenza season and will be evaluated by testing of 
a, preferably, nasopharyngeal (NP) specimen for influenza (see Section 5.2.5, ILI 
Symptom Assessment and Documentation Training). A parent or LAR of the subject or a 
delegate is contacted weekly to capture these cases throughout the study, resulting in 30 
to 45 ILI reminder calls. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 41 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
The study has a treatment period and a follow-up period. For subjects with a previous 
influenza vaccination history, the treatment period begins at the time of vaccination and 
ends 28 days after vaccination and will consist of 2 clinical visits and one reminder call to 
complete the Subject diary card. The follow up period begins 28 days after vaccination 
and ends at the time of study completion visit. For subjects without or unknown previous 
influenza vaccination history, the treatment period begins at the time of first vaccination 
and ends 28 days after the second vaccination and will consist of 3 clinical visits and two 
reminder calls to complete the Subject diary card, one after each vaccination. The follow 
up period begins 28 days after second vaccination and ends at the time of study 
completion visit. All subjects, irrespective of previous influenza vaccination history, will 
receive 1 safety follow-up call 90 days after last vaccination during the follow up period 
and the follow-up period will conclude with a study completion visit (clinic visit or call).  
All subjects aged 6 through 11 months at enrollment, irrespective of randomization to 
investigational or comparator group, will receive a dose of the MenC vaccine at the end 
of the study.  
Safety data collection will include standard solicited adverse event reporting via subject 
diary card for 7 days after each study vaccine administration, all unsolicited AEs for 28 
days after each vaccine administration, and special AE categories (SAEs, NOCDs, AEs 
leading to withdrawal, medically-attended AEs for 30 days after ILI onset) for the full 
duration of the study. In countries without a marketing authorization to use of Neisvac-C 
vaccine, safety (SAEs and NOCDs, and AEs leading to withdrawal) will be assessed 28 
days after the MenC dose (given at Visit 5). 
Two blood samples will be collected from a sub-set of subjects participating in each 
influenza season (maximum 222 per season), one prior to vaccination and one 28 days 
after last vaccination. The timing of blood sampling depends on the subject’s previous 
influenza vaccination history and is specified in Section 3.5, Collection of Clinical 
Specimen.  
Table 3.1 Not-previously influenza vaccinated subjects: Subjects not-previously 
vaccinated or with unknown influenza vaccination history 
Age 
Vaccine 
Visit 1 
Visit 2 
Visit 5  
6-11 months 
Investigational 
QIVc 
QIVc 
MenC vaccine  
Comparator 
MenC vaccine  
Saline 
MenC vaccine 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 42 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
≥ 12 months 
Investigational 
QIVc 
QIVc 
- 
Comparator 
MenC vaccine 
Saline 
- 
 
Table 3.2 Previously influenza vaccinated subject: Subjects previously vaccinated 
with at least two (2) influenza vaccine doses 
Age 
Vaccine 
Visit 1 
Visit 2 
Visit 4 
6-11 months 
N/A^ 
- 
- 
- 
≥ 12 months 
Investigational 
QIVc 
- 
- 
Comparator 
MenC vaccine  
- 
- 
^ Currently available influenza vaccines are not licensed below age of 6 months, and 
protocol will exclude any subjects who have received influenza vaccine in the past 6 
months. Therefore, all eligible subjects below 12 months of age will be considered as not-
previously influenza vaccinated for enrolment in the study. 
The subject’s previous influenza vaccination history is determined by assessment of the 
influenza vaccination history of the subject (see Section 5.1.2, Screening). Not-previously 
influenza vaccinated subjects are subjects that have not received two or more doses of 
influenza vaccine prior to the current influenza season, or who do not know their 
influenza vaccine history. These not-previously influenza vaccinated subjects are 
randomized to receive two study vaccinations separated by 28 days. Previously influenza 
vaccinated subjects are subjects with a history of at least two doses of an influenza 
vaccine prior to the current influenza season, and are randomized to receive 1 study 
vaccination.  
Each subject will participate until the end of the influenza season as defined in the 
protocol for the season in which the subject is enrolled but at least 180 days after last 
vaccination. 
Details of the study procedures and assessments are provided in Section 5, Study 
Procedures and Section 7, Assessments, respectively. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 43 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
3.2 
Study Period 
Each subject should expect to participate in study until the end of the influenza season, 
but at least 180 days after last vaccination (approximately six to nine months).  
3.3 
Blinding Procedures 
The trial is designed as an observer-blind study. During the treatment period of the study 
designated and trained unblinded nurse(s), physician(s), or other qualified health care 
professional will be responsible for administering the study vaccines to the subjects. They 
will be instructed not to reveal the identity of the study vaccines either to the subject’s 
parent(s)/LAR/delegate or to the investigative site personnel (i.e., investigator and study 
nurse) involved in the monitoring of conduct of the trial, except in an emergency if 
unblinding in IRT is not possible. Vaccine administration should be shielded from the 
subject’s parent(s)/LAR(s) and blinded study personnel. The unblinded personnel should 
not be involved in data collection or data review such as safety assessments and/or collect 
study data after the vaccinations. Study vaccines will be assigned through an Interactive 
Response technology system.  
 
3.3.1 Subjects 6 through 11 months old at enrollment 
To maintain the blind in the study, all subjects aged 6 through 11 months at enrollment 
will receive a MenC vaccine at visit 5. According to the MenC (Neisvac-C) vaccine 
prescribing information subjects that received their first dose < 12 months of age should 
receive a second dose, at least 6 months after the first dose, to complete their primary 
immunization. For subjects aged ≥12 months at first vaccination, only one dose of the 
MenC vaccine is necessary. To meet these requirements and to maintain the blind in the 
study, all subjects aged 6 through 11 months at enrollment will receive a dose of the 
MenC vaccine at visit 5.  
 
Except in the case of medical necessity, a subject’s treatment should not be unblinded 
without the approval of the Sponsor. In such instance, every effort should be made to 
contact the Sponsor prior to unblinding. If unblinding occurs, by either accidental 
unblinding or emergency unblinding for a serious adverse event, prior to completion of 
the study, the investigator must promptly contact the Sponsor and document the 
circumstances in IRT. In case of an emergency, the information can be retrieved by the 
Investigator from the IRT system either via web or phone (a 24/7 backup service). If the 
subject or blinded site staff is unblinded by the Investigator, the subject could be removed 
from an Analysis Set. 
 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 44 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Investigators, Seqirus study team, all laboratory personnel involved in processing samples 
and performing laboratory assays and others who are directly involved in the conduct of 
the trial or in the analysis of the final trial results, or have contact with study centers, will 
remain blinded to the treatment codes and interim analysis results until the database has 
been locked for final analysis. 
 
3.4 
Data Collection 
3.4.1 Data Collected from Subjects 
The following data will be collected from each subject over the duration of their study 
participation: 
• Informed Consent related information 
• Demographic Information (see Section 5.1.2, Screening). 
• Physical Examination Information (see Section 5.1.2, Screening). 
• Adverse Events (see Section 7.1, Safety Assessment). 
• Medical History (see Section 5.1.2, Screening). 
• Relevant Concomitant Medications (see Sections 5.1.2, Screening and 6.4, Prior and 
Concomitant Medications and Vaccines). 
• All Vaccination History (see Section 5.1.2, Screening). 
All data collected must only be identified using the Subject ID, as described in Section 
5.1.4, Randomization. 
3.4.2 Tools Used for Data Collection 
Data will be recorded in the Subject diary card and collected on electronic Case Report 
Forms (eCRFs). 
Subject Diary Card 
Paper Diaries (pDiaries), hereafter referred to as subject diary cards will be the only 
source document allowed for solicited local and systemic adverse events (including body 
temperature measurements, starting after the initial 30 minute post-vaccination period at 
the clinic. The following additional rules apply to documentation of safety information 
collected in the subject diary card. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 45 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
The Investigator or delegated staff should monitor the subject’s diary card status during 
the treatment period of the study for compliance and review any solicited local and 
systemic adverse events (see Section 7.1.1, Solicited Adverse Events for instructions for 
review of the subject’s diary card). The subject’s parent(s)/LAR/delegate will receive 
training on diary completion before entering data (see Section 5.2.2, Subject Diary Card 
Dispense and Training) 
1. No corrections or additions to the information recorded by the subject’s 
parent(s)/LAR/delegate within the subject diary card will be allowed after it is 
delivered to the site. 
2. Any blank or illegible fields on the subject diary card must be described as missing in 
the eCRF. 
Case Report Forms 
This study utilizes EDC system to collect study-related data from each subject. A trained 
healthcare professional is required to enter subject data in the eCRFs in English based on 
the (medical) information available in each subject’s source record. 
Data should be entered into the eCRF in a timely fashion following each subject’s clinic 
visit, study procedure, or phone call. Each subject’s eCRF may be compared with the 
subject’s source records by an approved study monitor (or designee) over the duration of 
the study in order to ensure data collection accuracy. 
The following additional rules apply to documentation of subject diary card information 
collected in the CRFs: 
1. The site must enter all readable entries in the subject diary card into the eCRF, 
including those values that may be biologically implausible (e.g. body temperature: 
400°C). 
2. Any illegible or implausible data should be reviewed with the subject’s 
parent(s)/LAR/delegate. If an underlying solicited or unsolicited adverse event is 
described on review with the subject, this should be described in the source document 
and reported as an unsolicited adverse event in the Adverse Event eCRF (e.g., if the 
subject above confirms body temperature of 40°C on the day in which body 
temperature: 400°C was written into his/her subject diary card, this fever of 40°C 
should be recorded in the Adverse Event eCRF). 
3. Any newly described safety information (including a solicited adverse event) must not 
be written into the subject diary card and must be described in the study file as a 
verbally reported adverse event. Any adverse event reported in this fashion must be 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 46 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
described as an unsolicited adverse event and therefore entered on the Adverse Event 
eCRF. 
Influenza-like illness Booklet 
If a subject experiences signs and symptoms that meet the protocol defined criteria for 
ILI, the subject’s parent(s)/LAR/delegate will be asked to document the subjects body 
temperature (a body temperature of ≥ 37.8°C (≥ 100.0°F), using the supplied 
thermometer) and the ILI symptom(s) in an ILI Booklet. The highest recorded body 
temperature of the subject for the day should be recorded. Instructions and explanations 
on ILIs and the Booklet are provided by a trained healthcare professional during the ILI 
Symptom Assessment and Documentation Training (see Section 5.2.5, ILI Symptom 
Assessment and Documentation Training). Subjects with ILI symptoms and its 
complications ought to be treated according to recent accepted (national) clinical 
standards. In countries, in the exceptional case where calls are not feasible, study site 
personnel may visit the subject’s homes to inquire about signs and symptoms of illness in 
the subject. 
3.5 
Collection of Clinical Specimens 
The following clinical specimens are required to be collected from subjects in this study: 
• Blood. 
• Nasopharyngeal swabs. 
Blood specimens are only drawn from subjects participating in the immunogenicity sub-
set. Nasopharyngeal swabs are only taken from those subjects that report a protocol 
defined ILI episode. 
Processing of each specimen should be completed by a trained healthcare professional 
and in accordance with the study-specific Clinical Specimen Laboratory Manual. Testing 
of clinical specimens will be performed by a Seqirus or a Seqirus designated (contracted) 
laboratory. Further additional detail is available in the study-specific Clinical Specimen 
Laboratory Manual. 
Blood Specimens 
A maximum of 5 mL sample of blood will be drawn from all subjects participating in the 
immunogenicity sub-set at visit 1 before vaccination, and 28 days after last vaccination. 
The blood volume will not exceed 5 mL at each time point in order to provide the 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 47 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
necessary serum volume (approximately half of the blood draw volume) for the serology 
assays. 
The blood will be used for immunological assays as measured by the HI and MN assay. 
Stored samples may be used for additional immunogenicity analyses using other assays, 
to further characterize the immune response. See Section 7, Assessments for additional 
details. 
The total amount of blood collected over the study period per subject will be 10 mL. 
Nasopharyngeal Specimens 
Subjects who experience symptoms meeting the per protocol defined ILI criteria will 
have a nasopharyngeal (NP) swab collected for evaluation of the presence of influenza 
virus by RT-PCR (see Clinical Specimen Lab manual). NP swab is the preferred swab 
method; other methods/routes are: nasal swab or oropharyngeal swab. 
All samples will also be cultured for the growth of the clinical strain of influenza obtained 
from subjects in order to conduct antigenic characterization (to determine whether the 
clinical isolate is antigenically matched, or not, to the influenza vaccine strain). See 
Section 7, Assessments for additional details. 
3.6 
Stopping/Pausing Guidelines 
An event-driven interim analysis may be performed by the Sponsor with the possibility to 
stop the trial early for efficacy. In addition, an independent Data Monitoring Committee 
(DMC) can make a recommendation as to whether the study should be stopped /paused if 
there is a safety concern. The predetermined stopping guidelines are described in Section 
3.7, Data Monitoring Committee and the DMC charter. 
Independent of the DMC, the Sponsor can halt the study at any time. If the study is 
halted, the Sponsor or delegate will promptly notify the Regulatory Authorities and 
Investigators, who will promptly inform the study subjects and local Ethics 
Committee/Institutional Review Board (EC/IRB) as per local regulations. Study 
vaccinations and further enrolment will only occur after written authorization is provided 
by the Sponsor in conjunction with a recommendation to proceed by the DMC and in 
consultation with the health authorities and EC/IRB, as appropriate. 
3.7 
Data Monitoring Committee 
An independent DMC will be utilized for the study for periodic evaluation of safety and 
efficacy data during the study. The members of the DMC shall have no involvement in 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 48 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
the design or conduct of the trial and no financial interest in the outcome of the trial. The 
DMC will comprise solely of non-Seqirus employees, and include medical experts and a 
biostatistician. The DMC will advise on a stop for efficacy only when the pre-specified 
criteria of the interim analysis are met, otherwise the DMC will recommend that the trial 
will continue as planned.  
A DMC charter will be written documenting the operational processes and the roles and 
responsibilities, including the timing of meetings, methods of providing information to 
and from the DMC, format and content of data to be reviewed, frequency and format of 
meetings, and membership requirements. Any unblinded data will be reviewed in closed 
sessions of the DMC, without participation of the Sponsor. All descriptions of these 
closed sessions will be unavailable to the Sponsor until study unblinding has occurred. 
All reports, following open sessions of blinded data review will be available to the 
Sponsor as appropriate. DMC recommendations will be expressed clearly to the Sponsor, 
at minimum in written communication. After reviewing safety and efficacy data, the 
DMC will recommend that enrolment be continued, halted temporarily (pending 
additional information from the Sponsor or modification to the study design) or halted 
permanently as specified in the DMC charter. 
3.8 
Premature Withdrawal from Study 
Subjects may withdraw at any time, or be dropped from the study at the discretion of the 
investigator should any untoward effects occur and/or for safety reasons. In addition, a 
subject may be withdrawn by the investigator or the Sponsor if he/she violates the study 
protocol and related procedures. The investigator or study coordinator must notify the 
Sponsor immediately when a subject has been withdrawn due to an adverse event. 
The circumstances above are referred to as premature withdrawal from the study, and the 
reason for premature withdrawal should be clearly documented and detailed in the source 
documentation. The investigator should make every attempt to evaluate the subject’s 
safety, including resolution of ongoing AEs, at the time of premature withdrawal. If a 
subject want to withdraw from the study before all doses are administered or prior to the 
last planned study visit, the subject will be asked to be followed for safety for the duration 
of the study. When a subject withdraws, or is withdrawn, from the study, the procedures 
described in Section 5.5.1, Early Termination Visit should be completed if possible. 
The reasons for premature withdrawal from the study include: Adverse event, death, 
withdrawal of consent, lost to follow-up, other, and protocol deviation. These reasons are 
described in greater detail below. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 49 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Adverse Event 
For any subject withdrawn from study participation prior to the planned study completion 
visit, it is important to determine if an AE was associated with the reason for 
discontinuing the study. This AE must be identified on the AE eCRF by indicating 
“Withdrawn from study due to AE”. Any ongoing AEs at the time of study withdrawal 
must be followed until resolution or stabilization.  
Subjects who develop a serious adverse event (SAE) judged to be possibly or probably 
related to the study vaccine, including hypersensitivity reactions, should not receive 
subsequent vaccination but the subject will be asked to be followed for safety for the 
duration of the study. 
If a medically-attended adverse event occurred within 30 days following a protocol 
definition of ILI, the event should also be reported on the AE eCRF page (see Section 7.1, 
Safety Assessment).” 
Death 
For any subject withdrawn from study participation due to death, this should be noted on 
the study completion eCRF and the associated SAE that led to the death must be reported 
on the (S)AE page. 
Withdrawal of Consent 
The subject’s parent(s)/LAR can withdraw consent for participation in the study at any 
time without penalty or loss of benefit to which the subject is otherwise entitled. Reason 
for early termination should be deemed as “withdrawal of consent” if the subject 
withdraws from participation due to a non-medical reason (i.e., reason other than AE). If 
the subject’s parent(s)/LAR intends to withdraw consent from the study, the investigator 
should clarify if the subject will withdraw completely from the study or if the subject will 
continue study participation for safety. If the subject requests complete withdrawal from 
the study, no further study interventions or data collection will be performed with the 
subject. 
In countries where the Health Insurance Portability and Accountability Act (HIPAA) is 
applicable, if a subject’s parent(s)/LAR withdraws consent but does not revoke the 
HIPAA authorization, the Sponsor will have full access to the subject’s medical records, 
including termination visit information. If a subject’s parent(s)/LAR revokes only the 
HIPAA authorization, the Sponsor will have full access to all of the subject’s medical 
records prior to the date and time of written revocation. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 50 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Lost to Follow-Up 
For subjects who fail to show up for planned visits (clinic or telephone contacts), or for 
three consecutive visits (clinic or (safety or diary) telephone contacts), or fail to reply to 
ILI reminder calls for 4 weeks, study staff are encouraged to make at least three 
documented attempts to contact the subject’s parent(s)/LAR by telephone and at least one 
documented written attempt to contact the subject’s parent(s)/LAR to encourage the 
completion of study completion procedures. These efforts to contact the subject should be 
recorded in the source document. The termination date for the subject to be captured on 
the study completion eCRF page is the date of the last successful contact (clinic visit or 
telephone) with the subject. 
Other 
Examples for subjects withdrawn from the study due to other reasons can include: 
Sponsor decision to terminate the study, subject meeting a pre-specified withdrawal 
criterion, subject discontinuation for insurance issues, moving, no time, etc. This reason 
should be noted in the Study Completion CRF page and any ongoing AEs at the time of 
study withdrawal must be followed until resolution/stabilization. 
Study Terminated by Sponsor 
If the clinical study is prematurely terminated by the Sponsor, the investigator is to 
promptly inform the study subjects and local EC/IRB and should assure appropriate 
therapy and follow up for the subjects. All procedures and requirements pertaining to the 
archiving of study documents should be followed. All other study materials (study 
medication/vaccines, etc.) must be returned to the Sponsor. 
Protocol Deviation 
A protocol deviation is any change, divergence, or departure from the study design or 
procedures of a study protocol. In general, subjects associated with protocol deviations 
may remain in the study unless continuation in the study jeopardizes the subject’s health, 
safety, or rights. Five main categories can be identified: 
• Subject randomized and did not satisfy entry criteria.  
• Subject developed withdrawal criteria during the study, but was not withdrawn. 
• Subject received the wrong treatment or incorrect dose. 
• Subject took an exclusionary concomitant medication. 
• Key study procedures missed or performed out of window. 
 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 51 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Protocol deviations might impact the analysis. Protocol deviations and its consequences 
are defined in the study Statistical Analysis Plan. Investigators will apply due diligence to 
avoid protocol deviations. Under no circumstances should the investigator contact Seqirus 
or its agents, if any, monitoring the study to request approval of a protocol deviation, as 
no authorized deviations are permitted. If the investigator feels a change to the protocol 
would improve the conduct of the study this must be considered a protocol amendment, 
and unless such an amendment is agreed upon by Seqirus and approved by the IRB/EC 
and health authorities it cannot be implemented. 
3.9 
End of Study 
Most clinical trials intended to support the efficacy/immunogenicity and safety of an 
Investigational Product proceed to full completion of planned sample size accrual.  
Evaluation of the primary and/or secondary immunogenicity/efficacy objectives requires 
the testing of biological samples from the study subjects, which can only be completed 
after all samples are collected. The last samples for the analysis of the primary and/or 
secondary objectives will be taken up to the end of the influenza season. For the purpose 
of this protocol, end of study is defined as the completion of the testing of such biological 
samples, to be achieved no later than 8 months after the date of last unscheduled visit by a 
subject who manifested signs of influenza-like-illness (ILI) during the protocol defined 
influenza season and from whom a NP sample was taken. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 52 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
4. 
SELECTION OF STUDY POPULATION 
4.1 
Inclusion Criteria 
In order to participate in this study, all subjects must meet ALL of the inclusion criteria 
described. 
1. Individuals of 6 through 47 months of age on the day of informed consent. 
2. Individuals whose parent(s)/LAR have voluntarily given written informed consent 
after the nature of the study has been explained according to local regulatory 
requirements, prior to study entry. 
3. Individuals who can comply with study procedures including follow-up1. 
4. Individuals in generally good health as per the Investigator’s medical judgement. 
Prior to receipt of second study vaccination, subjects must be evaluated to confirm that 
they are eligible for subsequent vaccination. If subjects do not meet the criteria of the 
original inclusion criteria listed above, they should not receive additional vaccinations. 
4.2 
Exclusion Criteria 
Each subject must not have: 
1. Acute (severe) febrile illness (see Section 4.3 Criteria for Delay of Vaccination). 
Enrollment could be considered if the fever is absent for 72 hours. 
2. History of any anaphylaxis, serious vaccine reactions or hypersensitivity, including 
allergic reactions, to any component of vaccine or medical equipment whose use is 
foreseen in this study. 
3. Clinical conditions representing a contraindication to intramuscular vaccination and 
blood draws. These may include known bleeding disorders, or treatment with 
anticoagulants in the 3 weeks preceding vaccination.   
4. A known history of Guillain-Barré Syndrome or other demyelinating diseases such as 
encephalomyelitis and transverse myelitis. 
 
1 A subject and parent(s)/LAR are considered to be able to comply if the Investigator judges that the subject 
can complete all study procedures such as subject diary card, return for all the follow-up visits, be available 
for telephone calls (if applicable), ILI booklet as scheduled in the study. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 53 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
5. Abnormal function of the immune system resulting from clinical conditions, which 
include: 
a. Known or suspected congenital or acquired immunodeficiency. 
b. Systemic administration of corticosteroids (PO/IV/IM) at any dose for more than 
14 days, within 90 days prior to informed consent. Topical, inhaled and intranasal 
corticosteroids are permitted. Intermittent use (one dose in 30 days) of intra-
articular corticosteroids is also permitted. 
c. Administration of antineoplastic and immunomodulating agents or radiotherapy 
within 90 days prior to informed consent. 
6. Received immunoglobulins or any blood products within 180 days prior to informed 
consent. 
7. Received an investigational or non-registered medicinal product within 30 days prior 
to informed consent, or intend to participate in another clinical trial during the study. 
8. Participated in this trial in a prior season or is discontinued after randomization in the 
current season. 
9. Study personnel, family and household members of study personnel should not 
participate. 
10. Any other clinical condition that, in the opinion of the investigator, might interfere 
with the results of the study or pose additional risk to the subject due to participation 
in the study. 
11. Received influenza vaccination or has had documented influenza disease in the last 6 
months prior to informed consent. 
12. Prior vaccination to prevent Neisseria meningitidis serogroup C disease or prior 
infection caused by this organism. 
13. Received any other vaccines than influenza vaccine within 14 days (for inactivated 
vaccines) or 28 days (for live vaccines) prior to study vaccination or who are planning 
to receive any vaccine within 28 days after study vaccination. 
Prior to receipt of second study vaccination, subjects must be evaluated to confirm that 
they are eligible for subsequent vaccination. If subjects meet any of the original exclusion 
criteria listed above or experienced severe tolerability issues after first study vaccination, 
they should not receive additional vaccinations. However, these subjects should be 
encouraged to continue study participation. This review of eligibility should be 
documented in the source document and the reason for not administrating a scheduled 
study vaccine should be documented in the eCRF. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 54 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
4.3 
Criteria for Delay of Vaccination 
There may be instances when individuals meet all eligibility criteria for vaccination yet 
have a transient infection which may warrant delay of vaccination: clinical signs of fever 
and/or body temperature elevation [≥ 38.0°C (≥ 100.4°F)) within 3 days prior to intended 
study vaccination], or use of antipyretics and/or analgesic medications within 24 hours 
prior to vaccination. Under such circumstances, a subject may be considered eligible for 
vaccination after the appropriate visit window has passed and inclusion/exclusion criteria 
have been rechecked and if the subject is confirmed to be eligible. In these instances, 
missing the visit window is not considered a protocol deviation. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 55 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
5. 
STUDY PROCEDURES 
The sections that follow provide an overview of the procedures that are to be followed in 
enrolling, evaluating, and following subjects who participate in this clinical study. Visits 
can be either clinic visits or safety follow-up telephone calls, as specified in the Table 
below and in the Time and Events Table 1.1 and 1.2. Not all study procedures are to be 
performed at all clinical visits or calls. The Time and Events Table 1.1 and 1.2 specifies 
which procedure should be performed at which visit. 
In the exceptional case where calls or clinic visits are not feasible in some countries, 
study site personnel may visit the subject’s homes to inquire about signs and symptoms of 
illness in the subject, collect a NP swab specimen or perform other study assessments 
(Table 5-1), when agreed upon by the Sponsor and in line with country specific 
requirements and/or regulations. 
Table 5-1 
Study Procedures 
Visit Category 
Procedures 
Pre-vaccination Procedure(s) 
Section 5.1 describes procedures to be followed 
prior to study vaccination: informed consent, 
screening, enrolment, and randomization 
Procedure(s) related to Vaccination 
Section 5.2 describes procedures to be followed 
during a clinic visit involving vaccination: blood 
draw, vaccination, 30 minutes observation, Subject 
diary card training, ILI Symptom Assessment and 
Documentation Training, next visit schedule, and 
diary reminder call 
Post-vaccination Visit(s)  
Section 5.3 describes activities after last 
vaccination: Follow up clinic visit and safety 
follow-up call 
Procedure(s) related to Protocol Defined ILI 
episodes 
Section 5.4 describes possible procedures to be 
followed: ILI Symptom Assessment and 
Documentation, ILI reminder calls, unscheduled 
visit, ILI follow-up call 
Study Completion Visit 
Section 5.5 describes procedures to be followed at 
study completion (may include early termination 
visit and MenC vaccine administration) 
 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 56 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
5.1 
Pre-vaccination Procedure(s) 
This section describes the procedures that must be performed for each potential subject 
prior to vaccination, including obtaining informed consent, screening, enrolment and 
randomization. 
5.1.1 Informed Consent 
"Informed consent" is the voluntary agreement of an individual or his/her LAR to 
participate in research. Consent must be given with free will of choice, and without undue 
inducement. The individual must have sufficient knowledge and understanding of the 
nature of the proposed research, the anticipated risks and potential benefits, and the 
requirements of the research to be able to make an informed decision. 
Informed consent following local IRB/EC guidance must be obtained before conducting 
any study-specific procedure (i.e., all of the procedures described in the protocol).  The 
informed consent process may be conducted up to 10 days prior to any study procedure 
on Visit 1 (see Section 13.2, Informed Consent Procedures) The process of obtaining 
informed consent should be documented in the subject source document in addition to 
maintaining a copy of the signed and dated informed consent. 
If a subject’s parent(s)/LAR is unable to read, an impartial witness should be present 
during the entire informed consent discussion. An impartial witness is defined as a person 
who is independent from study conduct, who cannot be unfairly influenced by those 
involved with the study, who attends the informed consent process if the subject or the 
subject's LAR cannot read, and who reads the informed consent form and any other 
written information supplied to the subject. After the written informed consent form and 
any other written information to be provided to subjects, is read and explained to the 
subject’s parent(s)/LAR and after the subject’s parent(s)/LAR has verbally consented to 
the subject’s participation in the study and, if capable of doing so, has signed and 
personally dated the informed consent form, the witness should sign and personally date 
the consent form. By signing the consent form, the witness attests that the information in 
the consent form and any other written information was accurately explained to, and 
apparently understood by, the subject’s parent(s)/LAR and that informed consent was 
freely given by the subject’s parent(s)/LAR. 
All subjects will sign a generic or a separate ICF which includes the possibility of being 
included into the immunogenicity sub-set study. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 57 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
5.1.2 Screening 
After an individual has consented to participate in the study and informed consent is 
signed, that individual will be given a unique Screening number. The subject’s unique 
Screening number will be documented in the Screening and Enrolment log. The eligibility 
of the subject will be determined based on the inclusion and exclusion criteria listed in 
Section 4, Selection of Study Population and evaluated during this screening procedure. 
Screening procedure(s) includes: 
• Demographic data. Prior to study enrolment, demographic data will be collected from 
the subject, including: sex, date of birth, race, ethnicity. These data will be written in 
the source document (see Section 9.1, Source Documentation) and must be 
documented in the eCRF. 
• Medical history. Relevant medical history will be collected, including but not limited 
to any medical history that may be relevant to subject eligibility for study 
participation and previous and ongoing illnesses or injuries. Medical history can also 
include any medical history that contributes to the understanding of an adverse event 
that occurs during study participation, if it represents an exacerbation of an underlying 
disease/pre-existing problem. Preferably medical history should be obtained from 
medical record review. In the exceptional case that medical record information is not 
available, medical history can be obtained by parent(s)/LAR verbal reporting. These 
data will be written in the source document (see Section 9.1, Source Documentation), 
including a confirmation that written medical records are not available, and must be 
documented in the eCRF. In general, worsening of a pre-existing event reported in the 
Medical History should be reported as an AE as described in Sections 5.1.2, 
Screening and 7.1.2, Unsolicited Adverse Events. 
• Prior and concomitant medications or vaccinations. If applicable, prior and 
concomitant medications or vaccinations taken prior to start of study should be 
collected by review of the subject’s medical record and vaccination card (see Section 
6.5, Prior and Concomitant Medications and Vaccines for further details). In the 
exceptional case that documentation of medication or vaccination history is not 
available, subject’s parent(s)/LAR verbal recall of prior medication or vaccination 
will be recognized as sufficient medical history; this attempt and information must be 
captured in the source documentation. If the parent(s)/LAR is unable to recall 
previous vaccination status, then they should be considered not-previously influenza 
vaccinated. These data will be written in the source document (see Section 9.1, Source 
Documentation) and must be documented in the eCRF. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 58 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
• The use of antipyretics and/or analgesic medications within 24 hours prior to 
vaccination must be identified and the reason for their use (prophylaxis versus 
treatment) must be described in the source document and Concomitant Medications 
CRF. The use of antipyretics/analgesics within 24 hours prior to vaccine 
administration is a reason to delay study vaccination (see Section 4.3, Criteria for 
Delay of Vaccination, and Section 6.5, Prior and Concomitant Medications and 
Vaccines). 
• Symptom-directed physical examination. An interview with the subject’s 
parent(s)/LAR will be performed before enrolment if the subjects has reported any 
complaints (review of systems). This interview is used to guide physical examination. 
A symptom-directed physical examination is to be performed by a qualified health 
care professional. As part of the physical examination, the following clinical signs: 
weight, height and body temperature should be measured and documented in both the 
source and eCRF by a trained healthcare professional allowed by institutional policy 
including a check of general appearance. If body temperature is ≥ 38.0°C (≥ 100.4° F) 
at the time of screening, vaccination must be postponed (see Section 4.3, Criteria for 
Delay of Vaccination). These data will be written in the source document (see Section 
9.1, Source Documentation). Should the physical assessment reveal any abnormal 
values or events, these must be documented in the eCRF. 
In the event that the individual is determined ineligible for study participation, he/she is 
considered a screen failure. The reason for screen failure must be documented in the 
Screening and Enrolment log. If the individual is determined to be eligible for the study, 
he/she will be enrolled into the study. 
5.1.3 Enrolment 
After signing the informed consent form, if an individual is determined to be eligible for 
study participation, the investigator will enroll the subject and enter the Subject ID into 
the EDC system. The Subject ID will be the subject’s unique identification number for all 
eCRFs and associated study documentation that will be used for duration of the study. 
After enrollment, the Screening ID ceases to be used and remains in the Screening and 
Enrolment Log only. 
5.1.4 Randomization 
All enrolled subjects will be randomly assigned to one of the two study groups (QIVc or 
comparator) in a pre-specified ratio of 1:1, with stratification factors such as age cohort (6 
through 23 months / 24 through 47 months, with a at least 30% of the subjects between 6 
through 23 months of age and at least 30% of the subjects between 24 through 47 months 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 59 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
of age), previous influenza vaccination history. For immunogenicity assessments, a sub-
set of subjects (a maximum of 222 subjects per influenza season) will be assigned to the 
immunogenicity sub-set at a 1:1 ratio to QIVc or comparator respectively with 
stratification factors such as age cohort, and previous influenza vaccination history. 
Enrolled subjects will be randomized through a randomization and trial supply 
management (RTSM) system. The list of randomization assignments is produced by the 
RTSM system and approved by Seqirus according to applicable Seqirus Standard 
Operating Procedure (SOP). 
If for any reason, after signing the informed consent form (ICF), the subject who is 
eligible and enrolled fails to be randomized, this is called a randomization failure. Further 
guidance is provided in the CRF Instructions and the early termination study procedures 
must be applied. The reason for all randomization failures should be recorded in the 
Screening and Enrolment Log and in the source document as specified in the Source Data 
Agreement (SDA). The information on subjects who are randomization failures should be 
kept distinct from subjects who are screen failures, as described in Section 5.1.2, 
Screening. 
If for any reason, after randomization the subject fails to undergo treatment, this is an 
Early Termination and the early termination study procedures must be applied, including 
reason should be recorded in source document as specified in the SDA. The information 
on these Early Termination subjects should be kept distinct in the source documentation 
from randomization failures. 
5.1.5  Blood draw  
After randomization, but prior to vaccination, a maximum of 5 mL of blood will be drawn 
from subjects randomized into the sub-set for the immunogenicity testing (see Section 
3.5, Collection of Clinical Specimens. These data will be written in the source document 
(see Section 9.1, Source Documentation) and must be documented in the eCRF. 
5.2 
Procedure(s) related to Vaccination 
A study vaccine will be given on Visit 1 for previously influenza vaccinated subjects and 
on Visit 1 and 28 days (window: 0/+7 days) after first study dose for not-previously 
influenza vaccinated subjects using the study vaccine identified by the via IRT assigned 
Pack ID. The pack ID is the medication number printed on each individual kit and is 
specific to a treatment type (QIVc or MenC vaccine or saline for injection (placebo). 
Subjects aged 6 through 11 months at enrollment will receive a (second) dose of the 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 60 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
MenC vaccine during at Visit 5 (see Section 5.5, Study Completion Visit, and Section 
6.2, Vaccine Preparation and Administration).  
All serology samples for the immunogenicity sub-set should only be taken if the subjects 
are randomized in the immunogenicity sub-set. Samples are taken prior to vaccination on 
Visit 1 and 28 days after last study vaccine has been given. 
Prior to administration of each vaccination, confirm that the subject is eligible for 
additional study vaccinations and does not meet any criteria for delaying additional study 
vaccinations as described in Section 4, Selection of Study Population.  
5.2.1  Vaccination 
After completing the pre-vaccination procedures, administer the study vaccine to the 
subject according to the procedures described in Section 6.3, Vaccine Preparation and 
Administration. Observe the blinding procedures described in Section 3.3, Blinding 
Procedures. 
After each vaccination the subject will be observed for at least 30 minutes including 
observation for unsolicited adverse events, solicited adverse events, and body temperature 
measurement. Record all safety data collected during this time in the subject’s source 
document. 
5.2.2  Subject Diary Card Dispense and Training  
A subject diary card will be used in this study to document solicited adverse events after a 
study vaccine has been given. The subject diary card is the only source for collection of 
these data; therefore, it is critical that the subject’s parent(s)/LAR completes the subject 
diary card correctly. The subject’s parent(s)/LAR should be trained on how and when to 
complete each field of the subject diary card. 
The subject’s parent(s)/LAR should be (re-)trained on how to measure local solicited 
adverse reactions and body temperature. The measurement of solicited local adverse 
reactions is to be performed using the ruler provided by the site. 
The subject’s parent(s)/LAR should be instructed how to perform body temperature 
measurement using the thermometer provided by the site. If the subject feels unusually 
hot or cold during the day, the subject’s parent(s)/LAR should check body temperature. If 
the subject has fever, the highest recorded body temperature observed for that day should 
be recorded in the subject diary card. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 61 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Subject diary card training should be directed at the individual(s) who will perform the 
measurements of adverse events and who will enter the information into the subject diary 
card. This individual may not be the subject’s parent(s)/LAR, but if a person other than 
subject’s parent(s)/LAR enters information into the subject diary card, this person’s 
identity must be documented in the subject’s source record. Any individual that makes 
entries into the Subject diary card must receive training on completion of the subject diary 
card at the time of the visit. This training must be documented in the subject’s source 
record. 
It is preferred that the same individual should complete the subject diary card throughout 
the course of the study. 
5.2.3  Schedule the next study activity 
The site should schedule the next study activity: clinic visits, or safety follow-up call with 
the subject’s parent(s)/LAR. 
The subject’s parent(s)/LAR should be reminded of the next planned study activity. The 
subject’s parent(s)/LAR will be reminded to complete the subject diary card and to 
contact the site if there are any questions, and to contact the site immediately (or as soon 
as the subject is medically stable) if the subject has a medical condition that leads to a 
hospitalization or an emergency room visit or to a visit to/by a doctor or is of concern. 
Contact must be documented in the subject’s source record. 
5.2.4 Diary Reminder Calls  
Reminder telephone calls are not intended to be an interview for collection of safety data. 
If the subject’s parent(s)/LAR wishes to describe safety information, this information 
should only be collected by a trained healthcare professional at the site, and the safety 
data described must be written down in the subject’s source document and on an Adverse 
Events eCRF, as specified in Section 7.1, Safety Assessment.  
A subject diary card reminder call will be performed approximately 2 days after 
vaccination. The purpose of this call is to remind the subject’s parent(s)/LAR about 
completion of the subject diary card. The call follows the subject diary card Reminder 
Telephone Call Script provided to the site. The subject’s parent(s)/LAR should be 
reminded to contact the site via the telephone number provided in the informed consent to 
discuss medical questions. 
In countries, in the exceptional case where calls are not feasible, study site personnel may 
visit the subject’s homes to inquire about signs and symptoms of illness in the subject. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 62 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
5.2.5  ILI Symptom Assessment and Documentation Training 
The ILI Symptom Assessment and Documentation Training contains, at least, 
explanations and instructions for subject’s parent(s)/LAR how to recognize influenza-like 
illness, how to use the supplied thermometer to measure body temperature, how to report 
the ILI symptoms using the ILI Booklet, who to contact for an unscheduled clinic visit to 
have a nasopharyngeal (NP) swab collected, and not to use antiviral therapy prior to swab 
sampling. 
5.3 
Post-vaccination Visit(s) 
Post-vaccination visits will be performed 28 days, and 90 days after last vaccination 
(Section Time and Event Table). For some subjects aged 6 through 11 months at 
enrollment, also a Visit 6 is scheduled (approximately 28 days after MenC-dose at Visit 
5) (Section 5.5.2, Countries without a MenC market authorization). 
5.3.1 Follow-up Clinic Visit 
 
A follow-up clinic visit (e.g. Visit 2 or Visit 3, depending on influenza vaccination 
history) will be performed 28 days after last vaccination for all subjects. 
During the follow-up clinic visit, the subject diary card will be reviewed. No changes to 
the information recorded within the subject diary card are permissible. For details on the 
subject diary card as specified in Sections 3.4.2, Tools Used for Data Collection, 5.2.2, 
Procedure(s) related to Vaccination and 7.1.1, Solicited Adverse Events. The subject’s 
parent(s)/LAR will be interviewed to determine if any unsolicited adverse events occurred 
and if any concomitant medications or vaccines were taken/received in the time since the 
last clinic visit. The qualified health care professional reviewing these data will discuss 
the symptoms (if any) reported by the subject and will determine if any additional 
diagnoses and/or adverse events are present. Adverse events reported by the subject’s 
parent(s)/LAR at this follow-up clinic visit must be recorded in the subject's source 
document and on an Adverse Events eCRF, as specified in Section 7.1, Safety 
Assessment. 
Perform a symptom-directed physical examination if necessary according to symptoms 
the subject has reported. This is a physical examination that will include an examination 
of organ systems that are relevant to the investigator based on review of the subject’s 
reported adverse events, and concomitant medication use. This assessment may include: 
measurement of clinical signs, body temperature and a check of general appearance. The 
physical assessment must be performed by the investigator or designee of the investigator, 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 63 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
who is qualified to perform a physical assessment in accordance with their institutional 
policy. Corresponding information is documented in the subject’s source document. 
In subjects participating in the immunogenicity sub-set, a maximum of 5 mL of blood will 
be drawn for the immunogenicity testing (Section 3.5, Collection of Clinical Specimens). 
The site should schedule the next study activity, being safety follow-up call with the 
subject’s parent(s)/LAR. 
The subject’s parent(s)/LAR will receive a reminder of the next planned study activity. 
The subject’s parent(s)/LAR will be reminded to complete the subject diary card and to 
contact the site if there are any questions and to contact the site immediately (or as soon 
as the subject is medically stable) if the subject has a medical condition that leads to a 
hospitalization or an emergency room visit or to a visit to/by a doctor. Contact including 
the medical condition/event must be documented in the subject’s source record. 
5.3.2 Safety Follow-up Visit 
The Safety Follow-up visit is a telephone call performed 90 days after last vaccination 
(e.g. Visit 3 or Visit 4, depending on influenza vaccination history). In countries, in the 
exceptional case where calls are not feasible, appropriate study site personnel may visit 
the subject’s homes to inquire about signs and symptoms of illness in the subject. 
Safety follow-up calls are calls made to the subject’s parents(s)/LAR by qualified health 
care professional designated on the site’s roles and responsibilities log. These calls will 
follow a script which will facilitate the collection of relevant safety information. The 
subject’s parent(s)/LAR will be interviewed according to the script, and information 
relating to unsolicited adverse events including: serious adverse events (SAEs), new onset 
of chronic disease (NOCD), all medically-attended AEs within 30 days after the onset of 
ILI episode, and/or AEs leading to withdrawal, and concomitant medications or 
vaccinations associated with those events. All safety information described by the subject 
must be written down in a designated location within the source document and not written 
on the script used for the telephone call. The script will also include a question on ILI 
occurrence.  
The site should schedule the next safety follow-up call (if applicable) with the subject’s 
parent(s)/LAR. 
The subject’s parent(s)/LAR will be reminded to contact the site if there are any questions 
and to contact the site immediately (or as soon as the subject is medically stable) if the 
subject has a medical condition that leads to a hospitalization or an emergency room visit 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 64 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
or to a visit to/by a doctor. Contact including the medical condition/event must be 
documented in the subject’s source record. 
5.4 
Procedure(s) related to Protocol Defined ILI episodes 
5.4.1  ILI Reminder Calls 
Active surveillance for per protocol defined ILI will be conducted weekly via a reminder 
call or during planned clinic visits, from Visit 1 until the end of the influenza season. The 
subject’s parent(s)/LAR will be asked via a checklist to determine if symptoms of ILI are 
present. The purpose of the reminder call is to trigger an unscheduled visit and 
nasopharyngeal (NP) swab collection. During every reminder call, the subject’s 
parent(s)/LAR will be instructed to report and visit the study site in case of an ILI episode 
as soon as possible (see Section 5.4.2, Unscheduled Visit(s)). The reminder calls are not 
intended to collect any clinical data. If during the ILI reminder call an ILI is identified, a 
visit to the study site should be planned as soon as possible, as described in Section 5.4.2, 
Unscheduled Visit(s). In countries, in the exceptional case where calls are not feasible, 
study site personnel may visit the subject’s homes to inquire about signs and symptoms of 
illness in the subject. 
5.4.2  Unscheduled Visit(s) 
An unscheduled visit describes a non-routine study visit triggered by a specific event: 
(onset of) ILI symptoms during active ILI surveillance  
Subject will be asked to come to the study site for an unscheduled visit within the first 24 
hours or as soon as possible following ILI onset to ensure optimal viral yield. Preferably, 
samples will be accepted if collected up to 6 days following the day of ILI onset. In the 
exceptional case that a clinic visit is not feasible, a home visit may be considered. 
The following procedures should be carried out during this unscheduled visit: 
a) The ILI symptoms and ILI Booklet will be reviewed and collected. The information 
should be mentioned in the subject’s source documentation and recorded on the ILI 
event eCRF. 
b) Subjects meeting the protocol defined criteria for ILI will have a nasopharyngeal (NP) 
swab collected for evaluation for the presence of influenza virus. A NP swab is 
strongly preferred sampling method to ensure consistency across the study population 
(see Clinical Specimen Lab Manual for detailed procedures for collecting, processing 
and shipping ILI swab samples). NP swabs should be taken prior to antiviral therapy. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 65 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
If an antiviral therapy has been given prior to swab sampling, this should be 
mentioned in the subject’s source documentation and recorded on the Concomitant 
Medication page in eCRF. Subjects with ILI symptoms and its complications ought to 
be treated according to recent accepted (national) clinical standards. 
c) The Investigator will record the subjects body temperature as part of the Physical 
Examination (see Section 5.1.2, Screening). 
d) Physical examination findings will be recorded in the medical source documents and 
Adverse Events eCRF. 
e) The use of relevant medications and the occurrence of medically-attended AEs within 
30 days after the onset of ILI episode will be assessed. 
f) ILI Symptom Assessment and Documentation Training including an ILI Booklet will 
be provided (see Section 5.2.5, ILI Symptom Assessment and Documentation) 
The site should schedule the ILI follow-up call with the subject’s parent(s)/LAR. 
The subject’s parent(s)/LAR will be reminded to contact the site if there are any questions 
and to contact the site immediately (or as soon as the subject is medically stable) if the 
subject has a medical condition that leads to a hospitalization or an emergency room visit 
or to a visit to/by a doctor. Contact including the medical condition/event must be 
documented in the subject’s source record. 
5.4.3  ILI Follow-up Call 
An ILI follow-up call will be performed at 30 (+7) days after protocol defined ILI onset, 
amongst subjects who have had their NP swab obtained. The subject’s parent(s)/LAR will 
be asked a set of questions to:  
a) Assess ILI symptoms and associated medications, if any. 
b) Assess medically-attended adverse events within 30 days after protocol defined ILI. 
c) Remind subject of next study activity. 
The subject’s parent(s)/LAR will be reminded to contact the site if there are any questions 
and to contact the site immediately (or as soon as the subject is medically stable) if the 
subject has a medical condition that leads to a hospitalization or an emergency room visit. 
Both contact and the medical condition/event must be documented in the subject’s source 
record. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 66 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
In countries, in the exceptional case where calls are not feasible, study site personnel may 
visit the subject’s homes to inquire about signs and symptoms of illness in the subject. 
5.5 
Study Completion 
Study completion will occur at the per protocol defined end of the influenza season but at 
least 180 days after last vaccination, except for some subjects aged 6 through 11 months 
at enrollment (see Time and Events Table and Section 5.5.2, Countries without MenC 
market authorization). For all subjects, the study completion visit is a telephone call by a 
qualified health care professional, or in an exceptional case a clinic or home visit 
performed by a qualified health care professional.  
Subjects aged 6 through 11 months at enrollment, irrespective of treatment allocation, 
will receive a dose of the MenC vaccine at Visit 5.  
The date of study completion is the date of the last contact (clinic or home visit or 
telephone call) in which the subject’s health status was assessed or, in cases where the 
subject does not agree to any further safety follow-up, it is the date consent is withdrawn. 
This date should be recorded in the source documents and on the study completion eCRF 
page. For visit procedures to be performed for a subject whose planned study 
participation ends prematurely, please see Section 5.5.1, Early Termination Visit. 
During the telephone call or clinic/home visit, the following procedures will be 
performed: Interview of subject’s parent(s)/LAR to collect potential: medically-attended 
AEs within 30 days after the onset of ILI episode, NOCDs, AEs leading to withdrawal, 
SAEs, ILIs and interview to collect concomitant medications/ vaccinations.  
If during the study completion visit, ILI symptoms are reported by the parent/LAR  and if 
the onset of the ILI is within (≤) 6 days before the study completion visit, an NP swab 
should be collected from the subject for influenza testing and study staff will document 
the ILI in the subject’s source records and on the ILI eCRF (see procedures described in 
Section 5.4.2  Unscheduled Visit(s). Should an ILI be identified and a NP swab taken, it 
is recommended to postpone the study completion visit, to allow for the ILI follow-up 
visit to occur. In these instances, missing the study completion visit window is not 
considered a protocol deviation. Should the subject have experienced a protocol defined 
ILI for which an NP swab was obtained, please collect the information of any medically-
attended adverse events which have occurred within 30 days after the onset of the of ILI. 
If study completion is after the end of influenza season (i.e. after active ILI surveillance), 
documentation of an ILI and collection of a swab is not applicable. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 67 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
For subjects who will receive a dose of the MenC vaccine (see Section 6.2, Vaccine 
Preparation and Administration) during Visit 5, the vaccine is administrated  according to 
the procedures described in Section 6.2, Vaccine Preparation and Administration, and the 
subject will be observed for at least 30 minutes.   
The site will review with the subject’s parent(s)/LAR the plan of when information 
relating to the subject’s participation in the study may be available (e.g., study results, 
treatment assignments). It will also be discussed how information relating to the subject’s 
participation in the study will be shared with the subject’s healthcare provider, if the 
subject’s parent(s)/LAR chooses to share this information. 
The site will complete the study completion eCRF page and this will mark the completion 
of the subject’s participation in the study. 
5.5.1 Early Termination Visit 
When a subject is withdrawn from treatment or withdraws from the study, the investigator 
will notify the Sponsor or Delegate and, when possible, will perform the procedures listed 
below. The reason(s) for the early termination will be included in the subject’s source 
documentation. If the early termination visit is a telephone call, collect as much 
information as possible. Early termination visits include subjects who were randomized 
but not treated. 
At the clinic or home visit or during the telephone call, the same procedures will be 
performed as during the study completion visit, see Section 5.5, Study Completion, if 
possible. In addition, if applicable, review of subject diary card, collection of subject 
diary card, interview of subject’s parent(s)/LAR to collect: unsolicited adverse events, 
medically-attended adverse events, NOCDs, AEs leading to withdrawal, SAEs, ILIs, 
interview of subject’s parent(s)/LAR to collect concomitant medications/ vaccinations, 
blood sampling for immunogenicity. Subject’ parent(s)/ LAR of subjects enrolled at the 
age of 6 through 11 months will be asked to return to the study site at least 6 months after 
last vaccination to receive a dose of the MenC vaccine. If the subject’s parent(s)/LAR is 
not willing to return, the consequences of not receiving this dose of the MenC- vaccine 
should be explained and discussions should be documented in the source documentation. 
The site will review with the subject’s parent(s)/LAR the plan of when information 
relating to the subject’s participation in the study may be available (e.g., study results, 
treatment assignments). It will also be discussed how information relating to the subject’s 
participation in the study will be shared with the subject’s healthcare provider, if the 
subject’s parent(s)/LAR chooses to share this information. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 68 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
The site will complete the study completion eCRF page and this will mark the completion 
of the subject’s participation in the study. 
5.5.2 Countries without MenC market authorization 
In countries where the MenC vaccine is not licensed for use, a Visit 6 for subjects aged 6 
through 11 months will be performed, at approximately 28 days after MenC vaccination 
at Visit 5 (see Time and Events Table). For these subjects, Visit 6 is the study completion 
visit. During Visit 6 safety data will be collected (SAE, NOCD, AE leading to 
withdrawal). Visit 6 may be performed as a telephone call. For all other subjects a Visit 6 
is not required.

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 69 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
6. 
TREATMENT OF SUBJECTS 
All vaccines associated with this study are to be stored separately from other vaccines and 
medications in a secure location under appropriate storage conditions with temperature 
monitoring. All vaccines associated with this study must be checked for expiration date 
and if it has experienced a temperature deviation prior to use. Expired vaccines or those 
that have experienced a temperature deviation must not be administered to subjects, as 
specified in Section 6.5, Vaccine Supply, Labeling, Storage and Tracking.  
6.1 
Study Vaccine(s) 
The term ‘study vaccine’ refers to those vaccines provided by the Sponsor, which will be 
evaluated as part of the study objectives. The study vaccines specific to this study are 
described below. 
Investigational Vaccine:  
Cell-derived seasonal quadrivalent influenza vaccine: The investigational vaccine is 
the cell-derived seasonal quadrivalent influenza vaccine (Flucelvax Quadrivalent/ 
Flucelvax Tetra, QIVc, Seqirus). 
The Flucelvax Quadrivalent/ Flucelvax Tetra vaccine is a is a sterile, slightly opalescent 
suspension in phosphate buffered saline. The dose to be administrated (0.5 mL) is 
formulated to contain a total of 60 µg hemagglutinin (HA) per 0.5 mL dose in the 
recommended ratio of 15 µg HA of each of the four (4) influenza strains recommended 
by WHO for inclusion in the quadrivalent vaccine formulation for the influenza season 
corresponding to the season of conduct of study. Each dose of Flucelvax Quadrivalent/ 
Flucelvax Tetra may contain residual amounts of MDCK cell protein (≤ 25.2 µg), protein 
other than HA (≤ 240 µg), MDCK cell DNA (≤ 10 ng), polysorbate 80 (≤ 1500 µg), 
cetyltrimethlyammonium bromide (≤ 18 µg), and β-propiolactone (< 0.5 µg), which are 
used in the manufacturing process. The 0.5 mL pre-filled syringes contain no preservative 
or antibiotics. 
A comprehensive review of the Flucelvax Quadrivalent/ Flucelvax Tetra vaccine is 
available in the Investigators Brochure supplied by Seqirus (or delegate). This document 
should be reviewed by the Investigator prior to initiating the study. 
Comparator vaccine(s): 
  
The comparator is NeisVac-C (MenC vaccine, Pfizer Limited), a Neisseria meningitidis 
serogroup C polysaccharide conjugate vaccine. A masking dose of placebo (saline for 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 70 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
injection) will be administered to subjects who required a 2-dose vaccination to maintain 
the blind in the study. 
Meningococcal (Group C) Conjugate Vaccine: A dose of 0.5 mL of the Neisseria 
meningitidis serogroup C polysaccharide conjugate vaccine (NeisVac-C, Pfizer Limited) 
will be administered as comparator vaccine. 
 
The NeisVac-C vaccine is a sterile, homogenous semi-opaque white to off-white 
suspension in a single dose syringe. Each dose of 0.5 mL NeisVac-C vaccine contains the 
following active ingredients: 10 µg of meningococcal group C polysaccharide conjugated 
with 10 to 20 µg of tetanus toxoid protein, absorbed to aluminium hydroxide (1.4 µg, 
equivalent to 0.5 µg aluminium), plus the following ingredients: sodium chloride and 
water (4.1 µg) for injection, Qs to 0.5 mL. NeisVac-C vaccine does not contain 
preservatives or antibacterial agent. 
 
A comprehensive review of the Neisvac-C vaccine is available in the Summary of Product 
Characteristics / Package Insert supplied by Seqirus (or delegate). This document should 
be reviewed by the Investigator prior to initiating the study. 
Placebo (Saline for injection): A dose of 0.5 mL of saline for injection (placebo) will be 
administrated as second dose in not-previously influenza vaccinated subjects randomized 
to the MenC comparator group (see Table 3.1, Not-previously influenza vaccinated 
subjects). 
Saline for injection is a clear, colorless liquid. Each dose of 0.5 mL saline for injection 
(placebo) contains the following ingredients: Sodium chloride, 4.5 mg; Water for 
Injection, Qs to 0.5 mL. 
6.2 
Vaccine Preparation and Administration 
The investigator or designee will be responsible for oversight of the administration 
vaccine to subjects enrolled in the study according to the procedures stipulated in this 
study protocol. All study vaccines will be administered only by unblinded personnel who 
are qualified to perform that function under applicable local laws and regulations for the 
specific study site. 
Detailed vaccine preparation and administration instructions will be provided to 
investigators prior to study start. 
PRECAUTIONS TO BE OBSERVED IN ADMINISTERING STUDY VACCINE: 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 71 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Prior to vaccination, subjects must be determined to be eligible for study vaccination and 
it must be clinically appropriate in the judgment of the investigator to vaccinate. 
Eligibility for vaccination prior to first study vaccine administration is determined by 
evaluating the entry criteria outlined in protocol Sections 4.1, Inclusion Criteria and 4.2, 
Exclusion Criteria. 
Eligibility for subsequent study vaccination is determined by following the criteria 
outlined in Section 4.3, Criteria for Delay of Vaccination. 
The study vaccines should not be administered to individuals with known hypersensitivity 
to any component of these vaccines. 
Standard immunization practices are to be observed and care should be taken to 
administer the injection: Intramuscularly into the anterolateral region of the thigh (for 
subjects 6 through 11 months, in general) or in the deltoid region (for subjects ≥ 12 
months, in general). Before administering a vaccine, the vaccination site is to be 
disinfected with a skin disinfectant (e.g., 70% alcohol). Allow the skin to dry. DO NOT 
inject intravascularly or intragluteally. 
As with all injectable vaccines, trained medical personnel and appropriate medical 
treatment should be readily available in case of anaphylactic reactions following vaccine 
administration. For example, epinephrine 1:1000, diphenhydramine, and/or other 
medications for treating anaphylaxis must be available. 
6.3 
Vaccine Administration Error or Overdose of Vaccine 
A vaccine administration error is defined as receiving a dose of study vaccine that was not 
reconstituted as instructed or administered by a different route from the intended route of 
administration. An overdose of study vaccine (whether accidental or intentional) is 
defined when a dosage higher than the recommended dosage is administered in one dose 
of vaccine as per dosing regimen described in Section 6.1, Study Vaccines. 
An overdose would also occur if two doses of the study vaccine are administered within 
half the time of the recommended interval between doses, as defined in the protocol. 
Any vaccine administration error or overdose of study vaccine detailed in this protocol 
must be reported as an adverse event, and if the vaccine administration error or overdose 
is associated with a Serious Adverse Event (SAE), it must be reported as such within 24 
hours to the Sponsor. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 72 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
6.4 
Prior and Concomitant Medications and Vaccines 
All medications, vaccines and blood products taken or received by the subject within 1 
month prior to the start of the study are to be recorded on the Prior and Concomitant 
Medications eCRF. In addition, the following are considered prior medications for this 
protocol: all medication/vaccines described in the inclusion and exclusion criteria of this 
protocol including:  
a) Influenza vaccination in the last 6 months. 
b) Systemic administration of corticosteroids (PO/IV/IM) within 90 days prior to 
informed consent. Topical, inhaled and intranasal corticosteroids are permitted. 
Intermittent use (one dose in 30 days) of intra-articular corticosteroids is also 
permitted. 
c) Administration of antineoplastic and immunomodulating agents or radiotherapy 
within 90 days prior to informed consent. 
d) Received immunoglobulins or any blood products within 180 days prior to informed 
consent. 
 
The use of antipyretics and/or analgesic medications within 24 hours prior to vaccination 
must be identified and the reason for their use (prophylaxis versus treatment) must be 
described in the source document and Concomitant Medications eCRF. The use of 
antipyretics/analgesics within 24 hours prior to study vaccine administration is a reason to 
delay study vaccination, as described in Section 4.3, Criteria for Delay of Vaccination. 
Medications taken for prophylaxis are those intended to prevent the onset of symptoms. 
Medications taken for treatment are intended to reduce or eliminate the presence of 
symptoms that are present. 
Concomitant medications include all medications (including vaccines; with the exception 
of vitamins, minerals and alternative medicines) taken by/administered to the subject at 
and after enrolment continuing up to the end of the treatment period and must be 
documented on the Concomitant Medications eCRF. During the follow-up period, all 
vaccinations should be documented and only those concomitant medications are 
documented on the Concomitant Medications eCRF if associated with an SAE, 
medically-attended AEs within 30 days after the onset of ILI episode, NOCD, or AE 
leading to study withdrawal.  
A non-study influenza vaccination(s) is considered a protocol deviation if received during 
the study and may result in the subject being excluded from the Per Protocol Set (PPS). 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 73 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
The following additional treatments, if used within the treatment period, e.g. in case of 
medical need, represent a protocol deviation and may result in the subject being excluded 
from the Per Protocol Set (PPS): 
a) Cancer chemotherapy. 
b) Immunosuppressive agents or systemic corticosteroids at any dose (topical, inhaled 
and intranasal corticosteroids are permitted, also a single dose of intra-articular 
corticosteroids is permitted). 
c) Blood, blood products and/or plasma derivatives or any parental immunoglobulin 
preparation. 
d) Any non-study investigative agents. 
 
When recording concomitant medications/vaccines, they should be checked against the 
study entry and continuation criteria in Section 4, Selection of Study Population to ensure 
that the subject should be enrolled/continue in the study. 
6.5 
Vaccine Supply, Labeling, Storage and Tracking 
The Sponsor will ensure the following: 
• Supply the study vaccine(s). 
• Appropriate labeling of all study vaccines in compliance with the legal requirements 
of each country where the study is to be performed. 
• Appropriate storage and distribution of study vaccines. 
The investigator must ensure the following: 
• Acknowledge receipt of the study vaccines by a designated staff member at the site, 
including: 
- 
Confirmation that the vaccines were received in good condition and in the right 
amount. 
- 
Confirmation to the Sponsor that temperature range during shipment from the 
Sponsor to the investigator’s designated storage location in the correct range (2°C 
to 8°C / 35.6°F to 46.4°F). 
- 
Report any temperature deviation and do not use vaccines until further 
confirmation by the Sponsor or delegate that the vaccines are authorized for use. 
• Proper storage of the study vaccines, including: 
- 
Storage in a secure, locked, temperature-controlled location. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 74 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
- 
Proper storage according to the instructions specified on the labels and in the 
Pharmacy Manual. 
- 
Appropriate record keeping and inventory of the study vaccines, including regular 
documentation of adequate storage temperature. 
• Appropriate management of the study vaccines, including: 
- 
Non-use of vaccines in case of temperature deviation, prior to receipt of 
authorization for use from the Sponsor or delegate. 
- 
Use only in accordance with the approved protocol. 
- 
Proper handling, including confirmation that the vaccine has not expired prior to 
administration. 
- 
Appropriate documentation of administration of vaccines to study subjects 
including: 
▪ 
Date, dosage, batch/lot numbers, expiration dates, unique identifying numbers 
assigned to subjects and study vaccines, and time of vaccine administration. 
This information will be maintained in an accountability log that will be 
reviewed by the site monitor. 
▪ 
Reconciliation of all vaccines received from the Sponsor. Reconciliation is 
defined as maintaining records of which and how many vaccines were 
received, which vaccines were administered to subjects, which vaccines were 
destroyed at the site, and which vaccines were returned to the Sponsor, as 
applicable. 
• Proper adherence to the local institutional policy with respect to destruction of study 
vaccines. 
• Complete record keeping of study vaccine use, wastage, return or destruction, 
including documentation of: 
- 
Copy of the site’s procedure for destruction of hazardous material. 
- 
Number of doses destroyed, date of destruction, destruction code (if available), 
method of destruction, and name of individual performing destruction. 
Vaccines that have been stored differently from the manufacturer’s indications must not 
be used unless the Sponsor provides written authorization for use. In the event that the use 
cannot be authorized, the Sponsor will make every effort to replace the vaccine supply. 
All vaccines used in conjunction with this protocol must be stored separately from normal 
hospital/practice stocks to prevent unintentional use of study vaccines outside of the 
clinical study setting. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 75 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Monitoring of vaccine accountability will be performed by the study monitor during site 
visits and at the completion of the study. 
At the conclusion of the study, and as appropriate during the course of the study, the 
investigator must ensure that all unused study vaccines, packaging and supplementary 
labels are destroyed locally (upon approval from Sponsor) or returned to the Sponsor. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 76 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
7. 
ASSESSMENTS 
7.1 
Safety Assessment 
The measures of safety used in this study are routinely used in clinical studies. They 
include a close vigilance for, and stringent reporting of, selected local and systemic 
adverse events routinely monitored in vaccine clinical studies as indicators of 
reactogenicity. 
An adverse event (AE) is defined as any untoward medical occurrence in a clinical 
investigation subject administered a pharmaceutical product at any dose that does not 
necessarily have to have a causal relationship with this treatment. Therefore, an AE can 
be any unfavorable and unintended sign (including an abnormal laboratory finding, for 
example), symptom, or disease temporally associated with the use of an investigational 
product, whether or not considered related to the investigational product. This definition 
includes intercurrent illnesses or injuries and exacerbation of pre-existing conditions. 
The period of observation for AEs extends from the time the subject signs informed 
consent until he or she completes the specified safety follow-up period or terminates the 
study early. AEs occurring after the informed consent form is signed but prior to 
receiving study vaccine/product will be documented as an adverse event and recorded 
within source document and eCRF. However, any AEs occurring prior to receipt of any 
study vaccine will be analyzed separately from “treatment emergent” AEs (AEs occurring 
after administration of the first study vaccine). 
Adverse events are collected as either solicited or unsolicited adverse events. Solicited 
events are derived from organized data collection systems, such as subject diary cards or 
interviews. 
7.1.1 Solicited Adverse Events 
The term “reactogenicity” refers to solicited signs and symptoms (“solicited adverse 
events”) occurring in the hours and days following a vaccination, to be collected by the 
subject’s parent(s)/LAR for seven (7) consecutive days after each vaccination (including 
the day of vaccination), using a pre-defined subject diary card. 
Each solicited adverse reaction and/or event is to be assessed and entered into the subject 
diary card, as described in Section 3.4.2, Tools Used for Data Collection. Each solicited 
adverse event is to be assessed according to a defined severity grading scale (see 
Statistical Analysis Plan (SAP) for further details). The following solicited adverse 
reactions and/or events are included in the subject diary card. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 77 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Solicited Local Adverse Reactions 
Injection site: 
• induration (hardness), in mm 
• erythema (redness), in mm 
• ecchymosis (bruising), in mm 
• tenderness, grading: 
o 0=none 
o 1=no interference with daily activity 
o 2=interferes with daily activity 
o 3=prevents daily activity 
 
Solicited Systemic Adverse Events 
• Change of eating habits 
o 0= None 
o 1= Eating less than normal for 1 - 2 feeds / meals 
o 2= Missed 1 or 2 feeds / meals 
o 3= Missed more than 2 feeds / meals 
• Sleepiness 
o 0=none 
o 1=shows an increased drowsiness 
o 2=sleeps through feeds / meals 
o 3=sleeps most of the time and it is hard to arouse him/ her 
• Vomiting (throwing up) 
o 0= None 
o 1= 1 - 2 times in 24 hours 
o 2= 3 - 5 times in 24 hours 
o 3= 6 or more times in 24 hours or requires intravenous hydration 
• Diarrhea (loose stools) 
o 0= Fewer than 2 loose stools in 24 hours 
o 1= 2-3 loose stools in 24 hours 
o 2= 4-5 loose stools in 24 hours 
o 3= 6 or more loose stools in 24 hours or requires intravenous hydration 
• Irritability 
o 0= None 
o 1= Requires more cuddling and is less playful than usual 
o 2= More difficult to settle 
o 3= Unable to console 
• Shivering 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 78 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
o 0= None 
o 1= Present but does not interfere with daily activity 
o 2= Interferes with daily activity 
o 3= Prevents daily activity 
 
Other Solicited Adverse Events 
The following are captured as “other solicited AEs”: 
• Use of analgesics/antipyretics are captured as “absent” or “present” and is also 
summarized by “for treatment” and “for prophylaxis”. 
• Fever derived from measured body temperature (defined as ≥ 38.0°C (≥ 100.4°F)). 
Measurement of temperature with a digital thermometer is preferred, the acceptable 
routes for temperature measurement in the study are: oral, axilla, ear or rectal. 
 
The study staff must review the data entered into the subject diary card as described in 
Section 3.4.2, Tools Used for Data Collection and Section 5.3.1, Follow-up Clinic 
Visit(s). All solicited local reactions and solicited systemic adverse events are considered 
causally related to vaccination.  
Note: Any solicited adverse reactions or event that meets any of the following criteria 
must be entered into subjects’ source document (see Section 9.1, Source Documentation) 
and also as an adverse event on the Adverse Event eCRF: 
• Solicited local adverse reaction or systemic adverse event that leads to a visit to a 
healthcare provider (medically-attended adverse event, see Section 7.1.3, Evaluation 
of Adverse Events). 
• Solicited local adverse reaction or systemic adverse event leading to the subject 
withdrawing from the study or the subject being withdrawn from the study by the 
investigator (adverse event leading to withdrawal, see Section 7.1.3, Evaluation of 
Adverse Events). 
• Solicited local adverse reaction or systemic adverse event that otherwise meets the 
definition of a serious adverse event (see Section 7.1.4, Serious Adverse Events). 
• If a solicited local adverse reaction or systemic adverse event continues beyond day 7 
after vaccination, it will also be recorded as an (unsolicited) AE on the AEs eCRF. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 79 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
7.1.2 Unsolicited Adverse Events 
All unsolicited adverse events need to be collected during the treatment period, which 
from informed consent to visit 2 for subjects with a history of previous influenza 
vaccination, or visit 3 for subjects with an unknown or without an influenza vaccination 
history (see Time and Event Table). During the follow-up period, from visit 2 or visit 3 
respectively depending on previous influenza vaccination history up to the study 
completion visit, only those unsolicited adverse events that either are medically-attended 
AEs occurred within 30 days after the onset of ILI episode, or lead to withdrawal or are 
Serious Adverse Events, need to be reported on the Adverse Events eCRF (see Time and 
Events Table). 
An unsolicited adverse event is an adverse event that was not solicited using a subject 
diary card and that was spontaneously communicated by a subject’s parent(s)/LAR who 
has signed the informed consent.  
Potential unsolicited AEs may be medically-attended (defined as symptoms or illnesses 
requiring hospitalization, or emergency room visit, or visit to/by a health care provider), 
or were of concern to the subject’s parent(s)/LAR. In case of such events, subject’s 
parent(s)/LAR will be instructed to contact the site as soon as possible to report the 
event(s). Unsolicited AE may also be reported during post-vaccination clinic visits or 
safety assessment phone calls. The detailed information about the reported unsolicited 
AEs will be collected by a qualified health care professional during the interview and will 
be documented in the subject’s source records. Depending on the timing and nature of the 
event, the AE should be reported in the AE CRF (see Section 7.1.3, Evaluation of 
Adverse Events, Section 7.1.4, Serious Adverse Events, and Section 7.1.5, Methods for 
Recording Adverse Events and Serious Adverse Events). 
An unsolicited AEs may be worsening of symptoms or illnesses reported in the Medical 
History eCRF (see Section 5.1.2, Screening). 
7.1.3 Evaluation of Adverse Events 
Every effort should be made by the investigator to evaluate safety information reported by 
a subject for an underlying diagnosis and to capture this diagnosis as the event in the AE 
page. In other words, the practice of reporting only symptoms (e.g., “cough” or “ear 
pain”) are better reported according to the underlying cause (e.g., “asthma exacerbation” 
or “otitis media”). 
The severity of events reported on the Adverse Events eCRF will be determined by the 
investigator as: 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 80 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Mild: 
transient with no limitation in normal daily activity. 
Moderate: 
some limitation in normal daily activity. 
Severe: 
unable to perform normal daily activity. 
The relationship of the study treatment to an AE will be determined by the investigator 
based on the following definitions: 
1. Not Related 
The AE is not related to an investigational vaccine if there is evidence that clearly 
indicates an alternative explanation. If the subject has not received the vaccine, the timing 
of the exposure to the vaccine and the onset of the AE are not reasonably related in time, 
or other facts, evidence or arguments exist that reasonably suggest an alternative 
explanation, then the AE is not related. 
2. Related 
a. Possibly Related 
The administration of the investigational vaccine and AE are considered reasonably 
related in time and the AE could be explained by exposure to the investigational vaccine 
or by other causes. 
b. Probably Related 
Exposure to the investigational vaccine and AE are reasonably related in time and no 
alternative explanation has been identified. 
The relationship of the study treatment to an unsolicited AE will be determined by the 
investigator.  
Note: solicited AEs will not be evaluated for relationship to study treatment, as in this 
study these solicited adverse events are considered by default related to the study vaccine. 
Grading for severity of solicited local and systemic AEs is described in the Statistical 
Analysis Plan (SAP). 
Adverse events will also be evaluated by the investigator for the co-existence of any of 
the other following conditions: 
• “Medically-attended adverse event”: an adverse event requiring hospitalization, or 
emergency room visit, or visit to/by a health care provider. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 81 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
• “New onset of chronic disease” (NOCD): an adverse event that represents a new 
diagnosis of a chronic medical condition that was not present or suspected in a subject 
prior to study enrolment. 
• AEs leading to withdrawal: adverse events leading to study or study vaccine 
withdrawal. 
If solicited or unsolicited adverse events have been reported and the subject’s 
parent(s)/LAR indicated that the symptoms required medical attendance or were of 
concern, the subject’s parent(s)/LAR must be contacted for further information. 
When the subject’s parent(s)/LAR is contacted for any of these reasons, the contact must 
be documented in the subject’s source documentation. 
All AEs, regardless of severity, will be monitored until resolution or until the investigator 
assesses them as chronic or stable. All subjects experiencing AEs - whether considered 
associated with the use of the study vaccine or not - must be monitored until symptoms 
subside and any abnormal laboratory values have returned to baseline, or until there is a 
satisfactory explanation for the changes observed, or until death, in which case a full 
pathologist’s report should be supplied, if possible. The investigator’s assessment of 
ongoing Adverse Events at the time of each subject’s last visit should be documented in 
the subject’s medical chart. 
7.1.4 Serious Adverse Events 
A serious adverse event (SAE) is defined as any untoward medical occurrence that at any 
dose results in one or more of the following: 
• Death. 
• Is life-threatening (i.e., the subject was, in the opinion of the investigator, at 
immediate risk of death from the event as it occurred); it does not refer to an event 
which hypothetically might have caused death if it were more severe. 
• Required or prolonged hospitalization. 
• Persistent or significant disability/incapacity (i.e., the event causes a substantial 
disruption of a person’s ability to conduct normal life functions). 
• Congenital anomaly/or birth defect. 
• An important and significant medical event that may not be immediately life 
threatening or resulting in death or hospitalization but, based upon appropriate 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 82 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
medical judgment, may jeopardize the subject or may require intervention to prevent 
one of the other outcomes listed above. 
Adverse events which do not fall into these categories are defined as non-serious. 
It should be noted that a severe adverse event need not be serious in nature and that a 
serious adverse event need not, by definition, be severe. 
Serious adverse events will be captured on the AE/SAE eCRF. All SAEs will be 
evaluated by the investigator for relationship of the event to study vaccine. SAEs that are 
judged to be possibly or probably related to the study vaccine should be reported to the 
Sponsor as related/suspected events. 
The relationship of the study treatment to an SAE will be determined by the investigator 
based on the following definitions: 
1. Related/suspected 
The SAE is judged by the investigator to be possibly or probably related to the study 
vaccine on the AE eCRF page (see Section 7.1.3, Evaluation of Adverse Events). 
2. Not Related 
The SAE is not related if exposure to the study vaccine has not occurred, or the 
occurrence of the SAE is not reasonably related in time, or the SAE is considered 
unlikely to be related to use of the study vaccine, i.e., there are no facts (evidence) or 
arguments to suggest a causal relationship. 
The relationship of the study vaccine to an SAE will be determined by the investigator. 
In addition, SAEs will be evaluated by the Sponsor or designee for “expectedness.” An 
unexpected AE is one that is not listed in the current Summary of Product Characteristics 
or the Investigator’s Brochure or an event that is by nature more specific or more severe 
than a listed event. 
In addition, a pre-existing event or condition that results in hospitalization should be 
recorded on the Medical History eCRF. The hospitalization itself should be reported in 
the AE/SAE eCRF. In general, worsening of a pre-existing event should be reported as an 
AE as described in Sections 5.1.2, Screening and 7.1.2, Unsolicited Adverse Events. If 
the onset of an event occurred before the subject entered the study (e.g., any pre-planned 
hospitalization for conditions like cosmetic treatments or for non-emergency routine visits 
for a pre-existing condition), the hospitalization would not lead to an AE being classified 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 83 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
as serious unless, in the view of the investigator, hospitalization was prolonged as a result 
of participation in the clinical study or was necessary due to a worsening of the pre-
existing condition.  
7.1.5 Methods for Recording Adverse Events and Serious Adverse Events 
Findings regarding Adverse Events must be reported on an Adverse Events eCRF, as 
specified in Section 7.1.1, Solicited Adverse Events. All findings in subjects experiencing 
AEs must be reported also in the subject's source document. 
All SAEs which occur during the course of the study, whether considered to be associated 
with the study vaccination or not, must be reported within 24 hours of the site becoming 
aware of the event to Seqirus or its designee. Specific instructions and contact details for 
collecting and reporting SAEs to Seqirus will be provided to the investigator. 
All SAEs are also to be documented on the AE/SAE eCRF. Any medication or other 
therapeutic measures used to treat the AE will be recorded on the appropriate eCRF(s) in 
addition to the outcome of the AE. 
After receipt of the initial report, representatives of Seqirus or its designee will contact the 
investigator if it is necessary to obtain further information for assessment of the event. 
All SAEs must be reported by the investigator to his/her corresponding EC or IRB or 
applicable regulatory authorities in accordance with institutional policy/regulatory 
requirements and adequate documentation of this notification must be provided to the 
Sponsor. 
Seqirus or its designee must also comply with the applicable regulatory requirement(s) 
related to the reporting of suspected unexpected serious adverse vaccine reactions (also 
known as SUSARs) to the regulatory authority(ies) and the IRB/EC. If a SUSAR or other 
safety signal relating to use of one of the study vaccines is reported to Seqirus or its 
designee, the Sponsor will communicate the information to the investigator and the 
investigator will be responsible for submitting this information to the EC or IRB and 
other relevant authorities. 
An RT-PCR confirmed influenza event in a subject randomized to and vaccinated with 
QIVc, can be considered as a case of vaccine failure. These cases will be entered in the 
database but not sent as an expedited report to applicable health authorities as these are 
related to the primary efficacy endpoint of the study and is an anticipated risk from 
participating in the study. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 84 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
7.1.5.1 
Post-Study Events 
Any SAE that occurs outside of the protocol-specified follow-up period and considered to 
be caused by the study vaccine must be reported to Seqirus or its designee. These SAEs 
will be processed by Seqirus or its designee, until 180 days after study completion. 
Instructions and contact details for collecting and reporting these suspected SAEs will be 
provided to the investigator. 
7.1.6 Safety Laboratory Measurements 
This study has no safety laboratory measurements. 
7.2 
Efficacy Assessment 
The case definition of influenza-like illness for this study is the presence of a temperature 
≥ 37.8°C (≥ 100.0°F) and at least one of the following symptoms on the same day: cough, 
sore throat, nasal congestion, rhinorrhea, earache or ear discharge and can occur at any 
time throughout the study and are to be reported immediately see Section 3, Study 
Design. 
Subjects who meet the protocol defined ILI criteria, will have a NP swab collected at an 
unscheduled visit. NP swab should be targeted for collection within the first 24 hours or 
as soon as possible after ILI onset (see Section 5.4, Unscheduled Visits). ILI onset is 
defined as the first day that the subject meets the protocol defined ILI criteria. The end 
date is defined as the date the subject does not meet the criteria anymore. A new ILI 
episode will only be taken into account after resolution of the previous one, as judged by 
the Investigator. As a guidance, another episode and swab sample should only be 
collected when the interval between the onset of protocol defined ILI to the next onset of 
protocol defined ILI is 14 days or more. 
Confirmation of influenza by RT-PCR from NP swab sample is necessary for the efficacy 
assessment in the study. In addition, all samples will also be cultured for the growth of the 
clinical strain of influenza obtained from the subject. Culture will allow to conduct 
antigenic characterization (to determine whether the clinical isolate is antigenically 
matched or unmatched to the influenza vaccine strain). Details on testing can be found in 
the Clinical Specimen Lab Manual. 
The case definition for moderate-to-severe influenza-like illness for this study is the 
presence of an ILI episode complicated by one of the following medically-attended AEs 
reported in the eCRF being either physician confirmed lower respiratory tract illness, or 
physician confirmed acute otitis media, or hospitalization in the Intensive Care Unit 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 85 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
(ICU), or physician-diagnosed serious extra-pulmonary complication of influenza, or 
supplemental oxygen requirement for more than 8 hours. Subjects with ILI symptoms and 
its complications ought to be treated according to recent accepted (national) clinical 
standards. 
Information on occurrences of any hospitalization, and administered or prescribed 
antibiotics or antivirals will be collected from the subject for the purposes of healthcare 
resource utilization assessment (regardless of whether or not the medical event, healthcare 
contact or the use of medications is considered to be directly linked to the ILI). Analyses 
on these endpoints will cover the period from ILI onset until 30 days after. 
For exploratory objectives, identification of influenza by genotypic methods may be 
conducted by a Seqirus or Seqirus designated (contracted) laboratory. 
7.3 
Immunogenicity Assessment 
The measures of immunogenicity used in this study are standard, i.e., widely used and 
generally recognized as reliable, accurate, and relevant (able to describe the quality and 
extent of the immune response). The measures are determined by the hemagglutination 
inhibition (HI) assay or microneutralization (MN) by titrating antibodies against the 
influenza strains homologous to the seasonal influenza vaccine (see Section 2, 
Objectives). The HI and MN tests will be conducted on serum samples collected 
immediately before first vaccination and 28 days after last vaccination, see Section 3, 
Study Design.  
To further characterize the immune response, additional exploratory immunogenicity 
analyses may be conducted on the immunogenicity sub-set using other tests such as an 
anti-neuraminidase assay. In case of exploratory immunogenicity analyses, the immune 
response will be characterized in a similar manner as described in Section 2, Objectives. 
Testing will be conducted by a Seqirus or Seqirus designated (contracted) laboratory in a 
blinded manner towards the treatment arm. Data will be captured and analyzed by an 
external CRO. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 86 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
8. 
STATISTICAL CONSIDERATIONS 
8.1 
Endpoints 
8.1.1 Primary Endpoint(s) 
8.1.1.1 
Primary Safety Endpoint(s) 
Not applicable. 
8.1.1.2 
Primary Efficacy Endpoint(s) 
Endpoints evaluating QIVc compared to a non-influenza vaccine: 
1. a. First occurrence of RT-PCR confirmed influenza, due to any influenza Type A 
and/or B virus regardless of antigenic match to the influenza strains selected for the 
seasonal influenza vaccine, occurring at > 14 days after the last vaccination and until 
the end of the influenza season, in association with protocol-defined ILI symptoms.  
 
1. b. First occurrence of culture confirmed influenza, due to influenza Type A and/or B 
virus antigenically matched by ferret antigenicity testing to the influenza strains 
selected for the seasonal influenza vaccine, occurring at > 14 days after the last 
vaccination and until the end of the influenza season, in association with protocol-
defined ILI symptoms. 
 
8.1.1.3 
Primary Immunogenicity Endpoint(s) 
Not applicable. 
8.1.2 Secondary Endpoint(s) 
8.1.2.1 
Secondary Safety Endpoint(s) 
The measures for assessing safety and tolerability are as follows: 
1. Percentage of subjects with solicited local and systemic AEs will be assessed for 7 
days following each vaccination in the QIVc group and the comparator group.  
 
2. Percentage of subjects with any unsolicited AEs will be assessed in the QIVc group 
and in the comparator group until 28 days after each vaccination. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 87 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
3. Percentage of subjects with SAEs, NOCDs, AEs leading to withdrawal from the study 
or vaccination, and all medications associated with these events will be reported in the 
QIVc group and in the comparator group. 
4. Percentage of subjects with medically-attended AEs within 30 days after ILI onset 
will be reported in the QIVc group and in the comparator group. 
 
8.1.2.2 
Secondary Efficacy Endpoint(s) 
Secondary efficacy endpoints evaluating QIVc compared to a non-influenza vaccine: 
2. The efficacy endpoint for the objective 2 is first occurrence of culture confirmed 
influenza caused by influenza virus strains antigenically dissimilar to the influenza 
strains selected for the seasonal vaccine occurring at > 14 days after the last 
vaccination and until the end of the influenza season, in association with protocol-
defined ILI symptoms. 
 
3. The efficacy endpoint for the objective 3 is first occurrence of culture confirmed 
influenza due to any influenza Type A and/or Type B virus regardless of antigenic 
match to the influenza strains selected for the seasonal influenza vaccine, occurring at 
> 14 days after the last vaccination and until the end of the influenza season, in 
association with protocol-defined ILI symptoms. 
 
4. The efficacy endpoint for the objective 4 is first occurrence of RT-PCR confirmed 
moderate-to-severe influenza due to any influenza Type A and/or Type B virus 
regardless of antigenic match to the influenza strains selected for the seasonal 
influenza vaccine, occurring at > 14 days after the last vaccination and until the end of 
the influenza season. 
 
8.1.2.3 
Secondary Immunogenicity Endpoint(s) 
The measures for immunogenicity are determined by a haemagglutination inhibition [HI] 
and a microneutralisation [MN] assay prior to vaccination (Visit 1) and 28 days after last 
vaccination for all four influenza strains. For each assay the measures include: 
 
1. Pre and post-vaccination geometric mean titers (GMTs); 
2. Seroconversion rates (SCR): Defined as the percentage of subjects with either a 
prevaccination HI (or MN) titer < 1:10 and a postvaccination HI (or MN) titer ≥ 1:40, 
or a prevaccination HI (or MN) titer ≥ 1:10 and a ≥ 4-fold increase in postvaccination 
HI (or MN) titer; 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 88 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
3. Geometric mean ratio (GMR): GMR is the geometric mean of the fold increase of 
post-vaccination HI (or MN) titer over the pre-vaccination HI (or MN) titer.  
 
8.1.3 Exploratory Endpoint(s) 
All exploratory endpoints will be further defined in the SAP.  
8.2 
Success Criteria 
8.2.1 Success Criteria for Primary Objective(s) 
The primary objective of efficacy is considered achieved if efficacy is demonstrated for at 
least one of the two primary efficacy endpoints. 
8.2.1.1 
Success Criteria for Primary Safety Objective(s) 
There are no primary safety objectives in this study. 
8.2.1.2 
Success Criteria for Evaluation of Primary Efficacy Objective(s) 
The lower limit (LL) of the two-sided 97.5% confidence interval (CI) of the estimator of 
absolute vaccine efficacy (aVE) of QIVc versus comparator calculated from RT-PCR 
confirmed influenza cases in subjects 6 months through 47 months of age is above 0%. In 
case an interim will be performed the 97.5% CI will be adjusted accordingly. 
 
8.2.1.3 
Success Criteria for Primary Immunogenicity Objective(s) 
There are no primary immunogenicity objectives in this study. 
8.2.2 Success Criteria for Secondary Objective(s) 
8.2.2.1 
Success Criteria for Secondary Safety Objective(s) 
Not applicable. 
8.2.2.2 
Success Criteria for Secondary Efficacy Objective(s) 
Not applicable. 
8.2.2.3 
Success Criteria for Secondary Immunogenicity Objective(s) 
Not applicable. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 89 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
8.3 
Analysis Sets 
8.3.1 All Enrolled Set 
All screened subjects who provide informed consent and provide demographic and/or 
baseline screening assessments, regardless of the subject’s randomization and treatment 
status in the study and received a Subject ID. 
8.3.2 All Exposed Set 
All subjects in the enrolled set who receive a study vaccination. 
8.3.3 Safety Set 
Solicited Safety Set (solicited local adverse reactions, solicited systemic adverse 
events and other solicited adverse events) 
All subjects in the Exposed Set with any solicited adverse event data, indicating the 
occurrence or lack of occurrence of solicited adverse events (e.g., use of 
analgesics/antipyretics medication) i.e., a subject does not have to have any solicited 
adverse events to be included in this population. 
Unsolicited Safety Set (unsolicited adverse events) 
All subjects in the Exposed Set with unsolicited adverse event data. 
Overall Safety Set 
All subjects who are in the Solicited Safety Set and/or Unsolicited Safety Set. 
Subjects will be analyzed as “treated” (i.e., according to the study vaccine a subject 
received, rather than the study vaccine to which the subject may have been randomized). 
8.3.4 Full Analysis Set (FAS) Efficacy/Immunogenicity Set 
Full Analysis Set Efficacy  
All subjects in the All Enrolled Set who are randomized, receive a study vaccination and 
provide efficacy data. 
Full Analysis Set Immunogenicity 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 90 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
All subjects in the All Enrolled Set who are randomized, receive at least one study 
vaccination and provide immunogenicity data at Secondary Immunogenicity Objectives. 
In case of vaccination error, subjects in the FAS sets will be analyzed “as randomized” 
(i.e., according to the study vaccine a subject was designated to receive, which may be 
different from the study vaccine the subject actually received). 
8.3.5 Per Protocol (PP) Set Efficacy/Immunogenicity Set 
All subjects in the FAS Efficacy / Immunogenicity who: 
• Correctly receive the study vaccine (i.e., receive the study vaccine to which the 
subject is randomized and at the scheduled time points). 
• Have no protocol deviations leading to exclusion (see Section 8.3.8, Protocol 
Deviations) as defined prior to unblinding / analysis. 
• Are not excluded due to other reasons defined prior to unblinding or analysis (see 
Section 8.3.8, Protocol Deviations) 
PPS are sub-sets of FAS and should be always defined even if the objectives do not 
require it. 
Examples for subjects excluded due to other reasons than protocol deviations are: 
- 
Subjects who withdrew informed consent. 
- 
Subjects who develop an influenza infection in an influenza immunogenicity 
study. 
Exclusions will be considered by objective/time point, i.e., sometimes not all data of a 
subject but only part of the subject's data will be removed from the PPS analysis. 
8.3.6 Other Analysis Sets 
There are no additional analysis sets for analysis. 
8.3.7 Subgroups 
The efficacy analyses will be performed by stratifying for the following subgroups: 
• Subjects aged “6 through 23 months” and “24 through 47 months”. 
• Subjects “previously influenza vaccinated” and “not-previously influenza 
vaccinated”. 
• Subjects by race. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 91 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
• Subjects by sex. 
• Subjects by country or region. 
• Subjects by season/year treated. 
The immunogenicity analyses will be performed by stratifying for the following 
subgroups: 
• Subjects aged “6 through 23 months” and “24 through 47 months”. 
• Subjects with pre-vaccination HI (or MN) titer <1:10 and pre-vaccination HI (or MN) 
titer ≥ 1:10. 
• Subjects “previously influenza vaccinated” and “not-previously influenza 
vaccinated”. 
• Subjects by race. 
• Subjects by sex. 
• Subjects by country or region. 
• Subjects by season/year treated. 
 
The safety analyses will be performed by stratifying for the following subgroups: 
• Subjects aged “6 through 23 months” and “24 through 47 months”. 
• Subjects “previously vaccinated” and “not-previously vaccinated”. 
• Subjects by comparator (MenC or saline for injection). 
• Subjects by race. 
• Subjects by sex. 
• Subjects by country or region. 
• Subjects by season/year treated. 
 
Safety and immunogenicity analyses will also be performed by time periods as detailed in 
SAP. Any other additional analyses may be performed, as described in Statistical 
Analysis Plan (SAP). 
8.3.8 Protocol Deviations 
A protocol deviation is any change, divergence, or departure from the study design or 
procedures of a study protocol. A protocol deviation may be a reason to remove data from 
an analysis set at the time of analysis. CSR-reportable (major) protocol deviations will be 
defined as exclusionary from the analysis according to protocol objectives and endpoints, 
which will be specified in the Protocol Deviation Specifications to this study protocol. In 
some cases, exclusion of data may be due to a reason other than a protocol deviation, e.g. 
early termination. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 92 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
8.4 
Statistical Analysis Plan 
8.4.1 Analysis of Demographic and Baseline Characteristics 
In general, summary descriptive statistics of continuous data will be presented as number 
of observations, mean, standard deviation, median, minimum and maximum. For 
categorical variables, statistical summaries will include counts and percentages relative to 
the appropriate population. Two-sided 95% (or 97.5%) confidence intervals (CI) will be 
provided for descriptive statistics, as warranted. The 95% or 97.5% CI for percentages 
will be exact CIs based upon the binomial distribution. 
8.4.2 Analysis of Primary Objective(s) 
8.4.2.1 
Analysis of Primary Safety Objective(s) 
The study does not have primary safety objectives. 
8.4.2.1.1 Analysis of Extent of Exposure 
Not applicable. 
8.4.2.1.2 Analysis of Solicited Local, Systemic and Other Adverse Events 
Not applicable. 
8.4.2.1.3 Analysis of Unsolicited Adverse Events 
Not applicable. 
8.4.2.1.4 Analysis of Safety Laboratory Values 
Not applicable. 
8.4.2.2 
Analysis of Primary Efficacy Objective(s) 
8.4.2.2.1 Statistical Hypotheses for Primary Efficacy Objectives 
The primary efficacy analysis will be based on the Full Analysis Set (FAS). Eligible 
subjects for FAS analysis are subjects who are randomized and received at least one study 
vaccine, and will be analyzed according to their randomized study vaccine [intent-to-treat 
analysis]). Absolute vaccine efficacy will only be assessed for RT-PCR confirmed 
influenza episodes (primary efficacy objective 1a) and culture confirmed influenza 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 93 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
episodes (primary efficacy objective 1b) with first onset of illness occurring at > 14 days 
after the last vaccination (since clinical protection is not immediate after vaccination) 
until the end of the influenza season. Additionally, the primary objective will be evaluated 
in Per-Protocol Analysis Set (PPAS). 
Time-to-event methodology based on a proportional hazard model will be used for all 
efficacy analyses to estimate the hazard ratio (HR). Absolute vaccine efficacy (aVE) 
against first occurrence RT-PCR confirmed influenza cases will be determined using a 
standard formula: aVE = 1 - HR where HR is the hazard ratio for RT-PCR influenza 
confirmed cases in the QIVc group versus the comparator group. The HR will be 
estimated by a proportional hazards regression model, described in Section 8.4.2.2.3, 
Statistical Methods. For which the following null (H0) and alternative (H1) hypotheses 
will be tested: 
                    H0: 1 – HR ≤ 0 versus H1: 1 – HR > 0 
where HR is a hazard ratio of QIVc versus comparator and VE is vaccine efficacy.  
Success Criteria for the Multiple Primary Efficacy Objectives:  
The primary objective of efficacy is considered demonstrated if efficacy is demonstrated 
for at least one of the two primary efficacy endpoints, if the lower limit (LL) of the two-
sided 97.5% confidence interval (CI) of VE is greater than 0% in subjects 6 months 
through 47 months of age. 
In case an interim analysis will be performed the 97.5% CI will be adjusted accordingly. 
If an interim analysis is performed and the trial continues, then all the subsequent analysis 
will be tested at a reduced alpha level, i.e. what’s left from the interim analysis.  
Further details regarding the statistical methods and analyses are specified in the 
Statistical Analysis Plan (SAP). 
8.4.2.2.2 Analysis Sets 
The analysis population for primary vaccine efficacy analyses will be based on the 
Efficacy FAS and repeated on the Efficacy PPS (further details are given in Section 8.3, 
Analysis Sets). 
8.4.2.2.3 Statistical Methods 
For both primary efficacy objectives, the HR and the related 97.5% CI of HR, for onset of 
first RT-PCR confirmed influenza will be estimated by a proportional hazards regression 
model with treatment effect as a fixed effect and stratifying covariates as random effect:  

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 94 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
hi(t|X) = h0(t) exp(βTX + bTZ), with t denoting time to the influenza, β is the effect of 
treatment group indicated by X, b is random effect (assumed as a multivariable random 
gaussian variable with zero mean and diagonal covariance matrix), Z is random effect 
covariate (reflecting randomization strata, see SAP for further discussion of the covariates 
utilized).  
Subjects that did not experience an event during observation period and subjects that 
dropped out from the study during observational period will be censored (right-
censoring).  
The estimate of the hazard ratio, the respective estimate for absolute VE and the 
pertaining two-sided CIs will be calculated based on this model.  
If the study continues over several seasons, estimates will be also adjusted for the factor 
season (s). In case of one or two (interim) analyses, confidence levels at each stage will 
be adjusted to provide 97.5% overall coverage. 
For each of the multiple primary objectives, estimates for hazard ratio in Cox 
Proportional hazard (PH) model will be calculated using Maximum Likelihood (ML) 
method. In case of problems with convergence (algorithm does not converge or converges 
to infinite estimates) penalized ML approach will be used (Heinze and Schemper).  
Vaccine efficacy VE = 1 – HR, that is, 1- exp(𝛽)
̂  with 𝛽̂ with 100(1- α) percent 
confidence interval as: [1- exp(𝛽̂+ Z(s.e.(𝛽)
̂ ); 1- exp (𝛽̂- Z(s.e.(𝛽)
̂ )].  
Z is the 100(1- α) percent point of the standard normal distribution, and s.e. denotes the 
standard error of 𝛽. 
The hazard ratio is the predicted ratio of cases of Influenza A and or B disease in subjects 
receiving QIVc and comparator within each of the strata of interest. The term βg is the 
estimate of treatment effect (or regression coefficient) between QIVc and comparator 
within each of the stratum. 
The estimate of the hazard ratio, the respective estimate for absolute VE and pertaining 
two-sided 97.5% CIs will be calculated based on this model. If the study continues over 
several seasons, estimates will be also adjusted for the factor season(s). Factor site/center 
or country might be added to the model if appropriate. In case of more than one interim 
analysis confidence level for the estimates at the final stage will be adjusted. 
In case interim analyses will be performed a k-stages group - sequential test procedure for 
time-to-event data will be implemented. As the K-stage interim analysis for absolute VE 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 95 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
introduces a multiple test problem, alpha will be adjusted as described in Section 8.6, 
Interim Analysis via an error-spending function. For this group sequential test procedure 
parameters like information level and/or standard error at each stage will be calculated by 
the above described model and then used to calculate the actual group sequential test that 
compared the test statistic at each stage with the respective boundaries. Repeated CIs for 
each stage and also the final estimator and the respective CI can be retrieved by the group 
sequential test method to maintain simultaneous coverage probability.  
Further details of the statistical methods will be provided in the Statistical Analysis Plan 
(SAP). 
8.4.2.3 
Analysis of Primary Immunogenicity Objective(s) 
Not applicable. 
8.4.2.3.1 Statistical Hypotheses 
Not applicable. 
8.4.2.3.2 Analysis Sets 
Not applicable. 
8.4.2.3.3 Statistical Methods 
Not applicable. 
8.4.3 Analysis of Secondary Objective(s) 
8.4.3.1 
Analysis of Secondary Safety Objective(s) 
8.4.3.1.1 Analysis of Extent of Exposure 
The number of subjects actually receiving vaccination will be summarized by study 
vaccine group. 
8.4.3.1.2 Analysis of Solicited Local, Systemic and Other Adverse Events 
All solicited adverse events will be summarized according to defined severity grading 
scales.  

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 96 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Frequencies and percentages of subjects experiencing each adverse event will be 
presented for each symptom severity. Summary tables showing the occurrence of any 
local or systemic adverse event overall and at each time point will also be presented.  
Post-vaccination solicited adverse events reported for 7 days after each vaccination and 
will be summarized for the intervals day 1-3, day 4-7, day 1-7 by maximal severity and 
by vaccine group, excluding the 30-minute measurement, which will be summarized 
separately. Injection-site erythema, ecchymosis and induration will be summarized 
according to categories based on linear measurements: Type I: none (0 mm), any (1-<10 
mm, 10-25 mm, 26-50 mm, >50 mm); Type II: Grade 0 (< 10 mm), any (10-25 mm, 26-
50 mm, >50 mm) (see Statistical Analysis Plan (SAP) for further details).  
Injection site tenderness and systemic adverse events (except fever) occurring up to 7 
days after each vaccination will be summarized according to “mild”, “moderate” or 
“severe” categorization. For the definition of severity grades see Section 7.1.3 of the 
protocol and Statistical Analysis Plan (SAP). 
Each solicited local and systemic adverse event will also be further summarized as “none” 
versus “any”. “Any” will include reactions with a diameter of at least 1 mm.  
Implausible measurements (for further definition see SAP) will be left out of the analysis. 
Use of antipyretics and analgesics will be summarized by frequency, by type of use 
(prophylactic versus treatment) and percentage of subjects reporting use. 
Body temperature will be summarized by 0.5°C and 1.0°C increments from 36.0°C up to 
≥ 40°C and will be broken down by route of measurement and by age cohort. 
8.4.3.1.3 Analysis of Unsolicited Adverse Events 
This analysis applies to all adverse events occurring during the study, judged either as 
probably related, possibly related, or not related to vaccination by the investigator, 
recorded in AE eCRF, with a start date on or after the date of first vaccination. AE 
starting prior to the first vaccination will only be listed. The original verbatim terms used 
by investigators to identify adverse events in the eCRFs will be mapped to preferred 
terms using the MedDRA dictionary. The adverse events will then be grouped by 
MedDRA preferred terms into frequency tables according to system organ class. 
All reported adverse events, as well as adverse events judged by the investigator as at 
least possibly related to study vaccine, will be summarized according to system organ 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 97 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
class and preferred term within system organ class. These summaries will be presented by 
vaccination group. 
When an adverse event occurs more than once for a subject, the maximal severity and 
strongest relationship to the study vaccine group will be counted. 
Separate summaries will be produced for the following categories:  
• Serious adverse events 
• NOCD 
• Adverse events that are possibly or probably related to study vaccine 
• Adverse event leading to study withdrawal or early termination 
• Adverse events leading to a medically-attended visit within 30 days after the onset of 
ILI episode 
• Adverse events leading to a medically-attended visit during the treatment period 
• Adverse events resulting in death. 
Data listings of all adverse events will be provided by subject. In addition, adverse events 
in the categories above will be provided as listed data. 
8.4.3.1.4 Statistical Hypotheses 
Not applicable. 
8.4.3.1.5 Analysis Sets 
The analysis population for safety analyses will be based on the Safety Set (further details 
are given in Section 8.3, Analysis Sets). 
8.4.3.1.6 Statistical Methods 
Not applicable. 
8.4.3.2 
Analysis of Secondary Efficacy Objective(s) 
8.4.3.2.1 Statistical Hypotheses for Secondary Efficacy Objectives 
The secondary measure of efficacy is the estimate of absolute efficacy of QIVc versus a 
comparator to prevent moderate-to-severe RT-PCR influenza confirmed cases caused by 
any influenza Type A and/or Type B virus. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 98 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Secondary efficacy objectives are not associated with any hypothesis testing. 
8.4.3.2.2 Analysis Sets 
The analysis population for all secondary efficacy objectives will be based on the 
Efficacy FAS and repeated on the Efficacy PPS (further details are given in Section 8.3, 
Analysis Sets). 
8.4.3.2.3 Statistical Methods for Secondary Efficacy Objectives 
The model specification used to estimate absolute vaccine efficacy for the secondary 
objectives is similar to the model used for the primary efficacy objectives. 
8.4.3.3 
Analysis of Secondary Immunogenicity Objective(s) 
8.4.3.3.1 Statistical Hypotheses 
No statistical testing will be performed for the comparative secondary immunogenicity 
objectives. 
8.4.3.3.2 Analysis Sets 
Secondary immunogenicity objectives will be evaluated based on the PPS 
Immunogenicity and FAS Immunogenicity (see Section 8.3, Analysis Sets). 
8.4.3.3.3 Statistical Methods for Secondary Immunogenicity Objectives 
All statistical analyses for HI (or MN titers) will be performed on the logarithmically 
(base 10) transformed values. Individual HI titers below detection limit (<10) will be set 
to half of that limit (5). 
Crude estimates for GMTs, GMRs and pertaining 2-sided 95% CIs will be calculated 
assuming log-normal distribution of the titers and will be completed by providing 
minimum, maximum and median titers for each study vaccine group. 
Binary data (i.e., percentages of subjects with seroconversion and with titer ≥ 1:40) will 
be summarized for each group using crude estimates and will be reported together with 2-
sided 95% CIs calculated according to Clopper’s and Pearson’s (1934) method. No 
multiplicity adjustment to the CI levels will be implemented. 
For immunogenicity data, it may be reasonable to consider missing immunogenicity 
values as missing completely at random (MCAR), i.e., not informative. Therefore, the key 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 99 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
secondary analysis will comprise a complete case analysis only, without introducing any 
bias. Imputation methods will not be used. 
8.4.4 Analysis of Exploratory Objectives 
The analysis of the exploratory objectives will be described in full detail in the Statistical 
Analysis Plan. 
8.5 
Sample Size and Power Considerations of Multiple Primary and Secondary 
Objectives 
This study is planned using a group sequential design, with one or more interim analyses 
for efficacy using O’Brien-Fleming efficacy bounds. The statistical test performed will 
depend on the number of RT-PCR confirmed influenza cases and the number of culture 
confirmed influenza cases, so the sample size estimate is only for operational reasons (an 
estimate of number of subjects needed to assess the endpoint).  
Statistical Considerations for Sample Size Calculations:  
For the primary efficacy endpoint 1a, assuming an attack rate in the comparator group of 
8% and an influenza vaccine efficacy (VE) of 40%, an estimated sample size of 
minimally 2,974 evaluable subjects (or 1,487 evaluable subjects per study group) with a 
minimum total of 191 cases are needed to have at least 90% power to reject the null 
hypothesis that the VE is less or equal to 0% at the significance level alpha=0.0125 and 
the risk of infection contained entirely within period covered by follow-up. For the 
primary efficacy endpoint for vaccine antigenically matched strains (1b), assuming an 
attack rate in the comparator groups of 4%, a VE of 50%, α=0.0125, a minimum of 3,446 
evaluable subjects and a minimum number of 104 cases are needed to have at least 90% 
power to reject the null hypothesis that the VE is less or equal to 0% at the significance 
level alpha= 0.0125. These results assume that the hazard ratio is constant throughout the 
study and that Cox proportional hazard regression is used for the analysis. Table 8.1 
summarizes the power calculations assumptions and the number of cases required to meet 
primary efficacy endpoints. 
 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 100 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Table 8.1. Power calculation for Multiple Primary Endpoints 
Primary  
Objective 
VE 
Success 
Criteria 
Assum
ed VE 
Alpha 
(α) 
Influenza 
attack 
rate in 
comparat
or group 
Power 
Approxim
ate 
evaluable 
subjects 
per 
Treatment 
Group 
Approxi
mate 
total 
subjects 
Enrolled 
Minimum 
number of 
ILIs to 
demonstrate 
LL 97.5% 
CI for VE is 
> 0% 
1a 
0% 
40% 
0.0125 
8% 
>90% 
1,487 
3,306 
191 
1b 
0% 
50% 
0.0125 
4% 
>90% 
1,723 
3,830 
104 
 
Accounting for 10% early dropout and uncertainty about the assumed parameters, an 
approximate number of 3,830 subjects are planned to be enrolled (or 1,915 subjects per 
study group) to demonstrate that the lower limit (LL) of the two-sided 97.5% CI for the 
VE is greater than 0% for the primary endpoint assessment. 
 
The study is designed to accrue a minimum of 191 RT-PCR confirmed influenza cases 
and a minimum of 104 culture confirmed influenza cases antigenically matched to the 
strains selected for the seasonal vaccine. If the overall/pooled influenza attack rate differs 
from the predicted and/or influenza strain circulation within a study season has drifted or 
shifted away from the strains selected for the seasonal vaccine, an adjustment of the 
prospectively specified number of cases, and number of subjects may be required. 
Extraneous real-life information, from (but not limited to) the influenza surveillance 
systems of the European Center for Disease Control (ECDC), US Center for Disease 
Control and Prevention (CDC) or World Health Organization (WHO) may be used to re-
assess the influenza event rate. 
Sample Size for Secondary Immunogenicity Objectives (Immunogenicity Sub-set): 
Per season, with a 1:1 allocation, approximately 100 evaluable subjects from the active 
arm and 100 evaluable subject from the comparator arm will be enrolled into the 
immunogenicity sub-set. Assuming a 10% drop out rate approximately 222 subjects will 
be allocated to the immunogenicity sub-set per influenza season.  
Sample Size for Safety: 
With a Safety Population of 1,723 evaluable subjects in the safety set of QIVc, AEs with 
population rates of 1 in 1,000 have an 82.2% probability of being detected. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 101 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Events with population rates of 1 in 575 have a 95% chance of being observed with 
n=1,723). Events with population rates of 1 in 2,000 have a 57.8% chance of being 
observed with n=1,723. 
Sample size calculations were performed using PASS v12.0.2. 
8.6 
Interim Analysis 
As the circulation of influenza viruses is seasonal and the event rates of influenza are 
difficult to predict, this study is group sequentially designed to allow for analyses of 
interim data to enable early study termination when a statistically robust demonstration of 
efficacy is observed.  
An event-driven interim analysis may be performed if deemed necessary by the Sponsor. 
In the event an interim is performed, the goal of the interim analysis is to be able to stop 
the study for early evidence of efficacy. For this analysis a restricted unblinding will be 
done, i.e. only external DMC members and Contract Research Organization (CRO) 
employees executing the unblinding receive access to the randomization codes and 
unblinded data for the purpose of preparing the interim analyses. Interim analyses are 
only intended to determine if the trial has met criteria for efficacy. Further details 
regarding the interim analysis will be described in the DMC Charter and the SAP. 
Primary Efficacy Analysis: 
Nasopharyngeal swab samples in this study will be analyzed in batches and the number of 
RT-PCR confirmed influenza cases and its antigenic match to the influenza vaccine strain 
will be reviewed on a regular basis (blinded review) throughout the study.  
An interim analysis for efficacy may be performed, if deemed necessary by the Sponsor: 
• 
If the number of RT-PCR confirmed influenza cases is less or equal to 95 overall, 
no interim analysis for efficacy will be done and the study will be extended 
because the probability to make a conclusion for efficacy is too low. 
• 
If the number of RT-PCR confirmed influenza cases is greater or equal to 96 but 
less than 191, an unblinded interim analysis for efficacy may be performed. To 
maintain the overall alpha, α = 1.25% (1-sided), for the hypotheses testing for the 
primary objectives, an error-spending-function will be used. The benefit of using 
an error-spending-function is that no maximum number of analysis stages and the 
timing of the analyses need to be pre-specified, what in practice means that the 
duration of the study in terms of number of seasons can be left open. In this case 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 102 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
α-boundaries, forming the adjusted probabilities for the type I error, are calculated 
using error-spending function and if the p-value for one primary objective is lower 
than the respective α-boundary the trial stops early (i.e., without reaching the 
targeted number of cases of 191) for efficacy. Otherwise, the trial continues 
enrollment. Decisions to stop or continue the trial will be made on the basis of 
discussions between the DMC and Senior Management. 
• 
If the number of RT-PCR confirmed influenza cases is greater or equal to 191, the 
study may be unblinded and the final analysis may be performed by the Sponsor. 
If the trial proceeds to the final analysis (upon reaching 191 cases) the boundaries 
for acceptance or rejection are identical to the assumed type I and type II errors for 
the overall design, and the trial stops to either reject or accept the null hypothesis 
of either one or / and the other of the primary objectives. 
In case the DMC states that the observed data provides already the full information level 
needed for the final test decision, then the final analysis can be done on full alpha level 
and no further enrollment is needed. However, if the decision of the group-sequential test 
is to continue the study then it is on the DMC to determine the number of subjects needed 
to be enrolled. The monitoring committee should not be influenced by the individual 
results of the study vaccine groups observed at an interim analysis stage when planning 
further subjects’ accrual or the times of future analysis. Only the overall number of cases 
is allowed to be used for further planning. The following formula for determination of 
sample sizes for further enrollment may be used:  
Ntotal = (Cplanned – Cobserved) / [(ERQIVc + ERcomp)/2],  
where Ntotal denotes the total number of subjects needed for further enrollment, Cplanned is 
the overall number of cases needed for the test, i.e 191 cases, Cobserved are the at that stage 
observed number of cases overall, and ER are the respective attack rates assumed for each 
group. A consideration of early dropout and uncertainty about assumed parameters will be 
accounted for number of enrolled subjects. The method of stopping rules given above is 
statistical and should be completed by clinical and strategic stopping rules that allow the 
DMC to make a decision on a broader picture of the data which includes safety endpoints 
and the other endpoints of the study. 
Stopping guidelines for efficacy and any additional details regarding the interim analysis 
will be specified in the DMC Charter and in the SAP. 
 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 103 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
9. 
SOURCE DOCUMENTATION, STUDY MONITORING AND AUDITING 
In order to ensure consistency across sites, study monitoring and auditing will be 
standardized and performed in accordance with the Sponsor’s or delegated contract 
research organization’s (CRO) standard operating procedures and applicable regulatory 
requirements (e.g., FDA, EMA, and ICH guidelines). 
Prior to enrolment of the first study subject, Seqirus or delegate will train investigators 
and/or their study staff on the study protocol, all applicable study procedures, 
documentation practices and all electronic systems. eCRFs supplied by the Sponsor must 
be completed for each enrolled subject (see Section 8.3.1, All Enrolled Set for definition 
of enrolled subject). Documentation of screened but not enrolled subjects must be 
maintained at the site and made available for review by the site monitor. Data and 
documents will be checked by the Sponsor and/or monitor. 
9.1 
Source Documentation 
Prior to the start of the study, the site staff participating in the study conduct will be 
instructed on what documents will be required for review as source documents. The kinds 
of documents that will serve as source documents will be agreed between Sponsor or 
delegate and investigator and designees and specified in the SDA prior to subject 
enrolment. 
In addition, source documentation must include all of the following: subject identification 
(on each page), eligibility and participation, proper informed consent procedures, dates of 
visits, adherence to protocol procedures, adequate reporting and follow-up of adverse 
events, documentation of prior/concomitant medication/vaccines, study vaccine 
receipt/dispensing/return records, study vaccine administration information, any data 
collected by a telephone conversation with the subject’s parent(s)/LAR and date of 
completion and reason. 
The subject’s parent(s)/LAR must also allow access to the subject’s medical records if 
available. Each subject’s parent(s)/LAR must be informed of this prior to the start of the 
study and consent for access to medical records may be required in accordance with local 
regulations. 
All safety data reported by subject’s parent(s)/LAR must be written down in source 
documents prior to entry of the data into eCRFs. If there are multiple sources of 
information (e.g., subject diary card, verbal report of the subject, telephone contact 
details, medical chart) supporting the diagnosis of an adverse event, these sources must be 
identified in the source documents, discrepancies between sources clarified, the ultimate 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 104 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
diagnosis must be justified and written in the source documents, and this diagnosis must 
be captured in the Adverse Event eCRF (AE eCRF). 
The subject diary card source data is hosted by a vendor engaged for this study, on behalf 
of the study investigators. Each investigator will be provided with a certified archive copy 
of all diary data relating to subjects at that site and must confirm it is readable.  
9.2 
Study Monitoring, Auditing and Source Data Verification 
Prior to enrolment of the first study subject, Seqirus or its designee (e.g., a CRO) will 
develop a Clinical Monitoring Plan to specify how centralized and/or on-site monitoring, 
including clinical specimens’ reconciliation, will be performed for the study. Study 
progress will be monitored by Seqirus or its designee as frequently as necessary to ensure: 
• that the rights and well-being of human subjects are protected, 
• the reported study data are accurate, complete, and verifiable from the source 
documents and 
• the conduct of the study is in compliance with the current approved 
protocol/amendment(s), GCP and applicable regulatory requirements. 
Contact details for the Seqirus team or its designee involved in study monitoring will be 
provided to the investigator. Study data recorded on eCRFs will be verified by checking 
the eCRF entries against source documents in order to ensure data completeness and 
accuracy as required by study protocol, except for those parameters which are specifically 
described in Section 7, Assessment being entered directly into the EDC system. 
Remote Source Data Verification may also be performed if allowed by the country and 
site regulations. The process of remote SDV activities will be detailed in study specific 
documents (e.g. Monitoring Plan) and must be conducted in full compliance with the 
applicable regulations, sponsor and CRO processes ensuring the protection of the subject 
data confidentiality. 
Data verification may also be performed through a centralized / remote review of 
data(e.g., checking for outliers or other anomalies) (see Source Data Agreement). 
Additional documents such as the investigator site file, pharmacy records, and informed 
consent documentation must also be available for review if requested. Arrangements for 
monitoring visits will be made in advance in accordance with the monitoring plan, except 
in case of emergency. 
The investigator and/or site staff must make source documents for subjects enrolled in 
this study available for inspection by Seqirus or its representative at the time of each 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 105 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
monitoring visit and Sponsor audits, when applicable. These documents must also be 
available for inspection, verification and copying, as required by regulations, by officials 
of the regulatory health authorities (e.g., FDA, EMA and others) and/or ECs/IRBs. The 
investigator and study site staff must comply with applicable privacy, data protection and 
medical confidentiality laws for use and disclosure of information related to the study and 
enrolled subjects. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 106 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
10. 
DATA MANAGEMENT 
10.1 
Data Entry and Management 
In this study, all clinical data (including, but not limited to, AE/SAEs, concomitant 
medications, medical history, and physical assessments), safety data, and immunogenicity 
data will be entered onto electronic case report forms (eCRFs) in a timely fashion by the 
investigator and/or the investigator’s dedicated site staff. Data is entered in eCRF using a 
secure electronic data capture (EDC) system and stored on a secure server, which is 
compliant with Title 21 Part 11 policies of the Code of Federal Regulations (FDA 1997). 
The data system includes password protection and internal quality checks. The EDC 
system will be designed and validated by the Sponsor prior to activation for data entry by 
sites. The investigator or designated delegate must review data entered and electronically 
sign the eCRFs to verify their accuracy. 
Access to the EDC system for data entry or review will require training and distinct 
individual access code assignments to those site staff members who will be entering study 
data and those involved in study oversight who may review study data. Data are collected 
within the EDC system, to which the Sponsor and site monitors have “read only” access. 
10.2 
Data Clarification 
As part of the conduct of the trial, the Sponsor may have questions about the data entered 
by the site, referred to as queries. The monitors and the Sponsor or its designated CRO 
are the only parties that can generate a query. All corrections and clarifications will be 
entered into the EDC system and will be identified by the person entering the information, 
the reason for the change, as well as the time of the changes made. If changes are made to 
a previously and electronically signed eCRF, the investigator must confirm and endorse 
the changes. 
10.3 
Data Protection 
Seqirus respects the subjects’ rights to privacy and will ensure the confidentiality of their 
medical information in accordance with all applicable laws and regulations. 
The Sponsor as Data Controller according to the General Data Protection Regulation 
(“GDPR”) on the protection of individuals with regard to the processing of personal data 
and on the free movement of such data confirms herewith compliance General Data 
Protection Regulation (“GDPR”) in all stages of Data Management. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 107 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
11. 
RECORD RETENTION 
Investigators must retain all study records required by Seqirus and by the applicable 
regulations in a secure and safe facility. The investigator must consult a Seqirus 
representative before disposal of any study records, and must notify the Sponsor of any 
change in the location, disposition, or custody of the study files.  
The sponsor specific essential documents should be retained until at least 2-years after the 
last approval of a marketing application in an ICH region and until there are no pending 
or contemplated marketing applications in an ICH region or at least 2-years have elapsed 
since the formal discontinuation of clinical development of the investigational product. 
These documents should be retained for a longer period however if required by the 
applicable regulatory requirement(s) or if needed by the sponsor (ICH E6 (R2)).  
“Essential documents” are defined as documents that individually and collectively permit 
evaluation of the conduct of a study and the quality of the data produced. These 
documents should be retained for a longer period, however, if required by the applicable 
national regulatory or institutional requirements. (ICH E6 (R2)). 
The sponsor should inform the investigator(s)/institution(s) in writing of the need for 
record retention and should notify the investigator(s)/institution(s) in writing when the 
trial related records are no longer needed. (ICH E6 (R2)). 
The principles of record retention will also be applied to the storage of laboratory 
samples, provided that the integrity of the stored sample permits testing. These laboratory 
samples will be securely stored for future testing at a global Seqirus or Seqirus 
controlled/contracted facility for up to 15 years and then destroyed, for purposes to 
conduct additional analyses needed related to the study, or ultimately for future analysis 
to further understand the immune response to the vaccine or to influenza disease. Only 
laboratory staff performing the testing will have access to these samples. By signing the 
ICF, the subject’s parent(s)/LAR agrees that samples will be retained for use limited to 
additional analyses related to this study. If the parent(s)/LAR also agrees to have the 
subject’s samples stored for future testing after the study is completed, this can be 
indicated on the ICF.

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 108 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
12. 
USE OF INFORMATION AND PUBLICATION 
Seqirus assures that the key design elements of this protocol will be posted in a publicly 
accessible database such as clinicaltrials.gov, and in compliance with current regulations. 
Seqirus also assures that key results of this clinical study will be posted in a publicly 
accessible database within the required time-frame from the end of study as defined in 
Section 3.9, End of Study. 
In accordance with standard editorial, ethical practices and current guidelines of Good 
Publication Practice (Graf 2009), Seqirus will generally support publication of 
multicenter studies only in their entirety and not as individual center data. In this case, a 
coordinating investigator will be designated by mutual agreement prior to the start of the 
study. The coordinating investigator will also sign the clinical study report on behalf of 
the principal investigators (CPMP/EWP/2747/00). Authorship will be determined by 
mutual agreement and in line with International Committee of Medical Journal Editors 
authorship requirements. Any formal publication of the study in which contribution of 
Seqirus personnel exceeded that of conventional monitoring will be considered as a joint 
publication by the investigator and the appropriate Seqirus personnel. 
Seqirus must be notified of any intent to publish data collected from the study and prior 
approval from Seqirus must be obtained prior to submission for publication. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 109 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
13. 
ETHICAL CONSIDERATIONS 
13.1 
Regulatory and Ethical Compliance 
The study will be conducted in compliance with the protocol, GCP and applicable 
regulatory requirement(s). 
This clinical study was designed and shall be implemented and reported in accordance 
with the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with 
applicable local regulations: including European Directive 2001/20/EC, US Code of 
Federal Regulations Title 21, ICH E6 (R2), and Japanese Ministry of Health, Labor, and 
Welfare, Seqirus codes on protection of human rights, and with the ethical principles laid 
down in the Declaration of Helsinki (European Council 2001, US Code of Federal 
Regulations, ICH 1997). 
13.2 
Informed Consent Procedures 
Eligible subjects may only be included in the study after the subject’s parent(s)/LAR 
provide written informed consent, as described in Section 5.1.1, Informed 
Consent/Assent. Before the start of the study, the investigator will have the informed 
consent and any other materials that will be provided to the subject’s parent(s)/LAR 
reviewed and approved by the IRB/EC. This review and approval will be documented and 
stored with other study documents. The investigator or designee must fully inform the 
subject or LAR of all pertinent aspects of the study. A copy of the written informed 
consent will be given to the subject’s parent(s)/LAR or the designee. The subject’s 
parent(s)/LAR/designee must be allowed ample time to ask about the details of the study 
and to make a decision as to whether or not to participate in the study. The subject and/or 
LAR must sign the consent form indicating their agreement to participate in the study 
before any study-related procedures are conducted. The informed consent process may be 
conducted up to 10 days prior to any study procedure on Visit 1. If the subject and/or 
LAR is unable to read and write, a witness must be present during the informed consent 
discussion and at the time of informed consent signature. 
Prior to the start of the study, Seqirus will provide to investigators a proposed informed 
consent form that complies with the ICH GCP guideline and regulatory requirements and 
is considered appropriate for this study. Any changes to the proposed consent form 
suggested by the investigator must be agreed to by Seqirus before submission to the 
IRB/EC and a copy of the approved version must be provided to the Seqirus monitor after 
IRB/EC approval. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 110 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
13.3 
Responsibilities of the Investigator and IRB/EC 
The protocol and the proposed informed consent form must be reviewed and approved by 
a properly constituted IRB/EC before study start. Properly constituted IRB/EC is defined 
in the integrated addendum to ICH E6: ICH Guideline for Good Clinical Practice E6(R2). 
A signed and dated statement that the protocol and informed consent have been approved 
by the IRB/EC must be given to Seqirus before study initiation. Prior to study start and at 
any time the protocol is amended during study conduct, the investigator is required to sign 
a protocol signature page confirming his/her agreement to conduct the study in 
accordance with these documents and all of the instructions and procedures found in this 
protocol and to give access to all relevant data and records to Seqirus monitors, auditors, 
Seqirus Clinical Quality Assurance representatives, designated agents of Seqirus, 
IRBs/ECs, and regulatory authorities as required. If an inspection of the clinical site is 
requested by a regulatory authority, the investigator must inform Seqirus immediately that 
this request has been made. 
The investigator also responsible for the following: 
• Maintaining a list of appropriately qualified persons to whom the investigator has 
delegated significant study-related duties. 
• Demonstrating the capability of recruiting the required number of suitable subjects 
within the recruitment period. 
• Demonstrating sufficient time and staffing to properly conduct and complete the study 
within the agreed study period. 
• Ensuring that all persons assisting with the study are adequately informed about the 
protocol, the investigational product(s), and their study-related duties and functions 
• Ensuring that qualified healthcare professionals are responsible for all study-related 
medical decisions and for ensuring appropriate medical care of subjects experiencing 
any adverse event related to the study. 
• If permission to do so is given by the subject’s parent(s)/LAR, ensuring that the 
subject’s primary healthcare provider is informed of the subject’s participation in the 
study. 
The investigator should not implement any deviation from, or changes of the protocol 
without agreement by the Sponsor and prior review and documented approval/favorable 
opinion from the IRB/IEC of an amendment, except where necessary to eliminate an 
immediate hazard(s) to study subjects, or when the change(s) involves only logistical or 
administrative aspects of the study (e.g., change in monitor(s), change of telephone 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 111 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
number(s)). In addition, the investigator, or person designated by the investigator, should 
document and explain any deviation from the approved protocol. 
The investigator may implement a deviation from, or a change of, the protocol to 
eliminate an immediate hazard(s) to study subjects without prior IRB/IEC 
approval/favourable opinion. As soon as possible, the implemented deviation or change, 
the reasons for it, and, if appropriate, the proposed protocol amendment(s) should be 
submitted: 
(a) to the IRB/IEC for review and approval/favorable opinion, 
(b) to the Sponsor for agreement and, if required, 
(c) to the regulatory authority(ies). 
13.4 
Protocol Amendments 
An amendment is a written description of change(s) to or formal clarification of a study 
protocol which may impact on the conduct of the clinical study, potential benefit of the 
clinical study, or may affect subject safety, including changes of study objectives, study 
design, subject population, sample sizes, study procedures, or significant administrative 
aspects. An administrative change of a study protocol is a minor correction or 
clarification that has no significant impact on the way the clinical study is to be conducted 
and no effect on subject safety (e.g., change of telephone number(s), logistical changes). 
Protocol amendments must be approved by Seqirus, health authorities where required, 
and the IRB/EC. In cases when the amendment is required in order to protect the subject 
safety, the amendment can be implemented prior to IRB/EC approval. Notwithstanding, 
the need for formal approval of a protocol amendment, the investigator is expected to take 
any immediate action required for the safety of any subject included in this study, even if 
this action represents a deviation from the protocol. In such cases, Seqirus should be 
notified of this action, the IRB/EC at the study site, and, if required by local regulations, 
the relevant health authority) should be informed within 10 working days. 
 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 112 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
14. 
REFERENCE LIST 
AAP Committee on Infectious Diseases. (2016) Recommendations for Prevention and 
Control of Influenza in Children, 2016–2017. Pediatrics; 138: e20162527. 
Ambrose CS, Levin MJ. (2012) The rationale for quadrivalent influenza vaccines. Human 
Vaccine Immunotherap; 8: 1–8. 
Belshe RB. (2010) The need for quadrivalent vaccine against seasonal influenza. 
Vaccine; 28: D45-53. 
Biere B, Bauer B, Schweiger B. (2010) Differentiation of influenza B virus lineages 
Yamagata and Victoria by real-time PCR. J Clin Microbiol; 48: 1425–7. 
Bourgeois FT, Valim C, Wei JC, et al. (2006) Influenza and other respiratory virus-
related emergency department visits among young children. Pediatrics; 118(1): e1-8. 
Ciani S, Huang QS, Ciblak MA, et al. (2015) Epidemiological and virological 
characteristics of influenza B: results of the Global Influenza B Study. Influenza and 
Other Respiratory Viruses; 9(Suppl. 1): 3–12. 
Claeys C, Zaman K, Dbaiboet G, et al. (2018) Prevention of vaccine-matched and 
mismatched influenza in children aged 6−35 months: a multinational randomised trial 
across five influenza seasons. Lancet Child Adolesc Health; In Press, Corrected Proof 
Available online 5 March 2018.  
Code of Federal Regulations (1997) Food and Drug Administration, U.S. Department of 
Health and Human Services: Title 21, Part 11: Electronic Records Electronic Signatures. 
Federal Register 62: 13464. 
Couch RB. (2007) Background and presentation of possible vaccine options. Presented at: 
Food and Drug Administration, Center for Biologics Evaluation and Research, Vaccines 
and Related Biological Products Advisory Committee Meeting; February 27-28, 2007; 
Washington, DC. 
Dewe W, Benoit A, Legrand C. (2013) Assessing vaccine efficacy in influenza clinical 
trials: challenges and difficulties. Expert Review of Clinical Pharmacology; 6: 403-411. 
European Parliament (2001): Directive 2001/20/EC of the European Parliament and of 
the Council of 4 April 2001. Official Journal of the European Communities. L 121/34-44. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 113 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Fiore AE, Uyeki TM, Broder K, et al. (2010) Prevention and control of influenza with 
vaccines: recommendations of the Advisory Committee on Immunization Practices 
(ACIP), 2010. MMWR Recomm Rep; 59: 1-62. 
Graf C, Battisti WP, Bridges D. (2009). Good publication practice for communicating 
company Sponsored medical research: the GPP2 guidelines. BMJ; 339: b4330. 
Hoberman A, Greenberg DP, Paradise JL, et al. (2003) Effectiveness of inactivated 
influenza vaccine in preventing acute otitis media in young children: a randomized 
controlled trial. JAMA; 290: 1608-16. 
Hu JJ, Kao CL, Lee PI, et al. (2004) Clinical features of influenza A and B in children 
and association with myositis. J Microbiol Immunol Infect; 37: 95–8. 
ICH E6 (R2). (2016) ICH Harmonised Tripartite ICH Guideline for Good Clinical 
Practices E6 (R2), EMA/CHMP/ICH/135/1995. 
ICH (1998) ICH Harmonised Tripartite ICH Guideline for Statistical Principles for 
Clinical Trials E9. Federal Register, 63 (179): 49583. 
Izurieta HS, Thompson WW, Kramarz P, et al. (2000) Influenza and the rates of 
hospitalization for respiratory disease among infants and young children. N Engl J Med; 
342: 232-9.  
Jacobs B, Young NL, Dick PT, et al. (2000) Canadian Acute Respiratory Illness and Flu 
Scale (CARIFS): Development of a valid measure for childhood respiratory infections. 
Journal of Clinical Epidemiology; 53: 793–9. 
Jain VK, Rivera L, Zaman K, et al. (2013) Vaccine for prevention of mild and moderate-
to-severe influenza in children. N Engl J Med; 369: 2481-91. 
Jansen AG, Sanders EA, Hoes AW, et al. (2008) Effects of influenza plus pneumococcal 
conjugate vaccination versus influenza vaccination alone in preventing respiratory tract 
infections in children: a randomized, double-blind, placebo-controlled trial. J Pediatr; 
153: 764-70. 
Jayasundara K, Soobiah C, Thommes E, et al. (2014) Natural attack rate of influenza in 
unvaccinated children and adults: a meta-regression analysis. BMC Infectious Diseases; 
14: 670. 
Jefferson T, Rivetti A, Di Pietrantonj C, et al. (2012) Vaccines for preventing influenza in 
healthy children. Cochrane Database Syst Rev;8: CD004879. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 114 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
Lambert LC, Fauci AS. (2010) Influenza Vaccines for the Future. N Engl J Med; 363: 
2036-44. 
Levine RJ. (1988) Ethics and Regulations of Clinical Research. New Haven: Yale 
University Press. 
Li-Kim-Moy JP, Yin JK, Heron L, et al. (2017) Influenza vaccine efficacy in young 
children attending childcare: A randomised controlled trial. J Paediatr Child Health; 53: 
47–54 
Mertz D, Fadel SA, Lam P, et al. (2016) Herd effect from influenza vaccination in non-
healthcare settings: a systematic review of randomised controlled trials and observational 
studies. Euro Surveill; 21: pii=30378.  
Orsi A, Colomba GME, Pojero F, et al. (2018) Trends of influenza B during the 2010-
2016 seasons in two regions of north and south Italy: the impact of the vaccine mismatch 
on influenza immunisation strategy. Hum Vaccin Immunother; 14: 523-31. 
Peltola V, Ziegler T, Ruuskanen O, et al. (2003) Influenza A and B virus infections in 
children. Clin Infect Dis; 36: 299–305. 
Pepin S, Dupuy M, Borja-Tabora C, et al. Intramuscular inactivated quadrivalent 
influenza vaccine is efficacious in naïve children aged 6 to 35 months: a large-scale, 
placebo-controlled trial. 6th conference of the European Scientific Working group on 
Influenza (ESWI) 2017, abstract no. SPA601, Riga, Latvia. 
Quiñones-Parra SM, Clemens EB, Wang Z, et al. (2016) A role of influenza virus 
exposure history in determining pandemic susceptibility and CD8 T cell responses. J 
Virol; 90: 6936–47. 
Rolfes MA, Goswami D, Sharmeen AT, et al. (2017) Efficacy of trivalent influenza 
vaccine against laboratory-confirmed influenza among young children in a randomized 
trial in Bangladesh. Vaccine; 35: 6967-76. 
Saunders NR, Tennis O, Jacobson S, et al. (2003) Parents’ responses to symptoms of 
respiratory tract infection in their children. CMAJ; 168: 25-30.  
Shepperd S, Perera R, Batesa S, et al. (2004) A children’s acute respiratory illness scale 
(CARIFS) predicted functional severity and family burden. Journal of Clinical 
Epidemiology; 57: 809–14. 

Seqirus 
Confidential 
Protocol V130_14 
03SEP 20 Final Version 3.0 
 
Page 115 of 115 
 
PRO-01 TEMP 06 / Atlas No. 293620 
Version No.4 / Version Date: January 29, 2015 
U.S. Department of Health and Human Services, Food and Drug Administration, CBER 
(2009): Guidance for Industry Patient-Reported Outcome Measures: Use in Medical 
Product Development to Support Labeling Claims. 
World Health Organization. (2012) Weekly Epidemiologic Record; 87: 461-76. 
59th World Medical Association General Assembly (October 2008) Declaration of 
Helsinki - Ethical Principles for Medical Research Involving Human Subjects. Seoul, 
Korea. 
 

Seqirus
Clinical Study Protocol V130_14 Amendment 1
15 NOV 18
Confidential
Page 1 of 4
PRO-01 TEMP 08 / Atlas No. XXXX
Version No. 3 / Version Date: May 5, 2014
CLINICAL STUDY PROTOCOL AMENDMENT
Study Number: V130_14
Protocol Title: A Phase III, Randomized, Observer-blind, Multicenter Study to Evaluate 
the Efficacy, Immunogenicity and Safety of Seqirus’ Cell-Based Quadrivalent Subunit 
Influenza Virus Vaccine (QIVc) Compared to a Non-Influenza Vaccine when 
Administrated in Healthy Subjects aged 6 Months through 47 Months
Amendment Number 1
Revised Protocol version 2.0 issued on 15 NOV 18
The present amendment reflects changes to Protocol version 1.0 issued on 22 JUN 18
Property of Seqirus*
Confidential
May not be used, divulged, published or otherwise disclosed without written
consent of Seqirus
*“Seqirus” includes all legal entities under which the company operates

Seqirus
Clinical Study Protocol V130_14 Amendment 1
15 NOV 18
Confidential
Page 2 of 4
PRO-01 TEMP 08 / Atlas No. XXXX
Version No. 3 / Version Date: May 5, 2014
DESCRIPTION OF CHANGE(S) AND RATIONALE:
This document describes the change to Neisseria meningitidis serogroup C vaccine as 
comparator for all subjects to provide benefit for all subjects in all countries. Furthermore, 
the amended protocol describes change to the blood draw volume and administrative 
updates observed during operational activity of the study and some miscellaneous 
(typographical) errors were corrected throughout the document. Finally, the exclusion 
criterion 12 was updated to ensure no subjects are enrolled into the study that have had 
prior N.meningitidis serogroup C disease.
CHANGE
LOCATION(S) OF 
CHANGE
RATIONALE FOR 
CHANGE
Each subject in the study 
will receive a Neisseria 
meningitidis serogroup C
(MenC) vaccine as 
comparator to the 
investigational vaccine 
(QIVc). Children without a 
history of previous 
influenza vaccination, will 
be randomized to either 
one dose of QIVc followed 
by a second dose of QIVc 
28 days later, or to a MenC
dose followed by a placebo 
28 days later. At the end of 
the study, at least 6 months 
after Visit 1, all subjects 
between 6 and 11 months 
of age will receive a dose 
of MenC at Visit 5.
Protocol Synopsis, Time 
and Event Table, Chapter 1 
(Background and 
Rationale), Chapter 2 
(Objectives), Chapter 3 
(Study Design), Chapter 5 
(Study Procedures), 
Chapter 6 (Treatment of 
Subjects), and Chapter 8 
(Statistical Considerations).
The comparator has been 
adjusted to provide benefit 
for all subjects in all 
countries throughout the 
study and to reflect 
regulatory feedback. In 
subjects who require two 
doses, MenC and placebo 
(saline for injection) will 
be administered separated 
by 28 days. Placebo will be 
used as masking dose to 
maintain the blind in the 
study. Similarly, MenC 
will be given to all subjects 
between 6 and 11 months 
at time of enrolment to 
preserve the blind.

Seqirus
Clinical Study Protocol V130_14 Amendment 1
15 NOV 18
Confidential
Page 3 of 4
PRO-01 TEMP 08 / Atlas No. XXXX
Version No. 3 / Version Date: May 5, 2014
CHANGE
LOCATION(S) OF 
CHANGE
RATIONALE FOR 
CHANGE
Some subjects, aged 6 
through 11 months at 
enrollment, enrolled in
countries without a 
Neisvac-C® (MenC, Pfizer 
Ltd.) market authorization, 
will have a scheduled clinic 
visit (Visit 5) to assess 
safety of the Neisvac-C -
vaccine given at Visit 6. 
Visit 6 is approximately 28 
days after the MenC dose
at Visit 5.
Protocol Synopsis, Time 
and Event Table, Chapter 1 
(Background and 
Rationale), Chapter 3 
(Study Design), and 
Chapter 5 (Study 
Procedures).
In some countries the 
MenC vaccine used, 
Neisvac-C® (Pfizer Ltd.) 
has no market 
authorization. In these 
countries, additional safety 
information will be 
collected for 28 days after 
MenC vaccination. The 
dosing schedule used in the 
study is according to the 
Summary of Product 
Characteristics (SPC)
approved by the UK 
regulatory authorities. This 
document will serve as the 
MenC reference document.
One of the exclusion 
criteria has been modified 
to: “Prior vaccination to 
prevent Neisseria 
meningitidis serogroup C 
disease or prior infection 
caused by this organism.”
Section 4.2 (Exclusion 
criteria).
Exclusion criterion number 
12 has been updated to also 
prevent subjects entering 
the study that have 
documented N.
meningitidis serogroup C 
disease prior to the study.

Seqirus
Clinical Study Protocol V130_14 Amendment 1
15 NOV 18
Confidential
Page 4 of 4
PRO-01 TEMP 08 / Atlas No. XXXX
Version No. 3 / Version Date: May 5, 2014
CHANGE
LOCATION(S) OF 
CHANGE
RATIONALE FOR 
CHANGE
The study includes blood 
sample collection at 2 time 
points with a maximum 
volume of 7 mL whole 
blood to be collected per 
time point. Blood draw 
volume has been lowered 
from 7 mL to 5 mL per 
blood draw.
Section 3.5 (Collection of 
Clinical Specimen), 
Section 5.1.5 (Blood draw), 
and Section 5.3.1 (Follow-
up Clinic Visit).
To reflect feedback 
received from investigators 
and ethical committees, the 
current blood draw volume 
is lowered from 7 mL to 5 
mL. This volume is 
sufficient to evaluate
immunogenicity against all 
4 homologous vaccine
strains using the 
haemagglutination 
inhibition (HI) assay: 3 
strains (Type A/H1N1, 
Type B/Yamagata and 
Type B/Victoria, and the
microneutralization (MN) 
assay: 1 strain (Type 
A/H3N2).
Acceptable measurements 
of body temperature now 
includes: oral, axilla, ear or 
rectal.
Time and Event Table, List 
of Definitions, Chapter 2 
(Objectives), Section 3.4.2 
(Tools Used for Data 
Collection),  Section 7.1.1 
(Solicited Adverse Events), 
and Section 7.2 (Efficacy 
Assessment).
To accommodate feedback 
from investigators, the 
route of temperature 
measurement in infants has 
been updated to: oral, 
axilla, ear and rectal to 
allow measurement of 
body temperature 
according local practices in 
the participating countries.
Correction of some 
miscellaneous 
(typographical) errors and 
clarifications to the 
protocol language.
Throughout the protocol.
Observations made during 
operational activity of the 
study and some 
miscellaneous 
(typographical) errors.

Seqirus
Clinical Study Protocol V130_14 Amendment 2
03 SEP 20
Confidential
Page 1 of 4
PRO-01 TEMP 08 / Atlas No. XXXX
Version No. 3 / Version Date: May 5, 2014
CLINICAL STUDY PROTOCOL AMENDMENT
Study Number: V130_14
Protocol Title: A Phase III, Randomized, Observer-blind, Multicenter Study to Evaluate 
the Efficacy, Immunogenicity and Safety of Seqirus’ Cell-Based Quadrivalent Subunit 
Influenza Virus Vaccine (QIVc) Compared to a Non-Influenza Vaccine when 
Administrated in Healthy Subjects aged 6 Months through 47 Months
Amendment Number 2
Revised Protocol version 3.0 issued on 03 SEP 20
The present amendment reflects changes to Protocol version 2.0 issued on 15 NOV18
Property of Seqirus*
Confidential
May not be used, divulged, published or otherwise disclosed without written
consent of Seqirus
*“Seqirus” includes all legal entities under which the company operates

Seqirus
Clinical Study Protocol V130_14 Amendment 2
03 SEP 20
Confidential
Page 2 of 4
PRO-01 TEMP 08 / Atlas No. XXXX
Version No. 3 / Version Date: May 5, 2014
DESCRIPTION OF CHANGE(S) AND RATIONALE:
This document describes an adjustment of the number of seasons over which the study is 
conducted and removes the requirement for a minimal number of subjects to be enrolled. 
Exploratory Objectives were added to include genotypic methods to characterize 
influenza cases and use of other assays to describe vaccine efficacy. Home visits are 
allowed for study assessments, in exceptional cases and remote source data verification is 
added as an option in view of the current pandemic situation. The amounts of residual 
proteins in the vaccine were corrected. Finally, administrative updates observed during 
operational activity of the study and some miscellaneous (typographical) errors were 
corrected throughout the document.
CHANGE
LOCATION(S) OF 
CHANGE
RATIONALE FOR 
CHANGE
The study is designed to 
accrue an approximate 
number of subjects and a 
minimum number of cases 
over several influenza 
seasons
Protocol Synopsis, Section 
1.3 (Rationale), Section 3.1 
(Overview of Study
Design), Section 8.5
(Sample Size and Power
Considerations), 8.6 
(Interim Analysis).
In time-to-event outcome 
studies, power depends on 
the number of events 
observed and is stopped 
when minimum of 
necessary number of events 
is reached. We modified 
the protocol language to 
reflect this more clearly. 
As the attack rate is not 
predictable, the update 
omits additional constraints
on a minimal number of 
subjects to be recruited or a 
minimal number of 
influenza seasons in which 
the study will be 
conducted.

Seqirus
Clinical Study Protocol V130_14 Amendment 2
03 SEP 20
Confidential
Page 3 of 4
PRO-01 TEMP 08 / Atlas No. XXXX
Version No. 3 / Version Date: May 5, 2014
CHANGE
LOCATION(S) OF 
CHANGE
RATIONALE FOR 
CHANGE
Added exploratory 
objectives:
To characterize the 
immune response by other 
assays.
To use genotypic methods 
to characterize circulating 
strains of influenza 
collected during the study.
Protocol Synopsis, Section
2.3 (Exploratory 
Objectives), Section 7.2 
(Efficacy Assessment) and 
7.3 (Immunogenicity 
Assessments), Section 
8.1.3 (Exploratory 
Endpoints) and 8.4.4. 
(Analysis of Exploratory 
Objectives)
To explore next generation 
influenza characterization 
methods.
In the exceptional case 
where calls or clinic visits 
are not feasible in some 
countries, study site 
personnel may visit the 
subject’s homes to inquire 
about signs and symptoms 
of illness in the subject, 
collect a NP swab 
specimen or perform other 
study assessments, when 
agreed upon by the 
Sponsor and in line with 
country specific 
requirements and/or 
regulations.
Protocol Synopsis, Table 
1.1 and 1.2, Section 5 
(Study Procedures).
To extend the possibility 
for home visits for other 
study assessments when 
deemed necessary e.g. in 
view of the current 
pandemic situation.
Remote Source Data 
Verification may be 
performed
Section 9.2 (Study 
Monitoring, Auditing and 
Source Data Verification)
To add the possibility when 
deemed necessary e.g. in 
view of the current 
pandemic situation.

Seqirus
Clinical Study Protocol V130_14 Amendment 2
03 SEP 20
Confidential
Page 4 of 4
PRO-01 TEMP 08 / Atlas No. XXXX
Version No. 3 / Version Date: May 5, 2014
CHANGE
LOCATION(S) OF 
CHANGE
RATIONALE FOR 
CHANGE
Each dose of Flucelvax 
Quadrivalent/ Flucelvax
Tetra may contain residual 
amounts of MDCK cell 
protein (≤ 25.2 µg), protein 
other than HA (≤ 240 µg)
Section 6.1 Study 
Vaccine(s)
To align the protocol text 
with the US PI and EU 
SPC. The amounts of 
proteins other than HA in 
the vaccine are increased as 
a consequence of the use of 
a different antigen potency 
assay agreed upon by the 
regulatory agencies in US 
and Europe.
The Data Monitoring 
Committee may 
recommend to stop the 
study for efficacy when at 
least one efficacy objective 
met the success criteria. 
The CI and overall alpha 
for hypothesis testing for 
the primary objectives 
during the interim analysis 
is adjusted to meet the 
overall coverage of 97.5%
CI and alpha is 1.25% (1-
sided), respectively
Protocol Synopsis, Section 
8.4.2.2.3 (Statistical 
Methods), Section 8.6 
(Interim Analysis)
This update aligns with the 
success criteria described 
in Section 8.2.1 (Success 
Criteria for the Primary 
Objective(s)) and the 
statistical methods
described in Section
8.4.2.2.1 (Statistical 
Hypotheses for Primary 
Efficacy Objectives)
Correction of some 
miscellaneous 
(typographical) errors and 
clarifications to the 
protocol language.
Throughout the protocol.
Observations made during 
operational activity of the 
study and some 
miscellaneous 
(typographical) errors.