An Randomized, Double-blind, Controlled Phase III Clinical Trial to Evaluate the Safety and Immunogenicity of Quadrivalent Influenza Vaccine in Healthy Subjects Aged 6 to 35months
Phase: PHASE3
Conditions: Seasonal Influenza
Sponsor: Sinovac Biotech Co., Ltd

        Phase III Clinical Trial of Quadrivalent Influenza Vaccine (Split Virion) in Children Aged 6-35 Months  
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Protocol No.: PRO-QINF-3005                                      Version No.:3.0  Version Date: Nov. 01, 2023 
 
 
Protocol title: A Randomized, Double-Blinded, Active-Controlled 
Phase III Clinical Trial to Evaluate the Safety and Immunogenicity 
of Quadrivalent Influenza Vaccine (Split Virion) in Children Aged 
6-35 Months 
 
Product name: Influenza Vaccine (Split Virion), Inactivated, Quadrivalent  
 
Sponsor: SINOVAC BIOTECH CO., LTD.  
 
Study Institute: 
Hubei Provincial Center for Disease Control and Prevention 
Anhui Provincial Center for Disease Control and Prevention 
 
Statistical agency: Beijing Key Tech Statistics Technology Co., Ltd. 
 
Protocol No.: PRO-QINF-3005 
 
Protocol Version Date: Nov. 01, 2023 
 
Version No.: 3.0 
 
Approved by: Zeng Gang 
 
Approver's Signature: 
 
Date of approval:    (MM/DD/YY) 
 
 
 

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Protocol No.: PRO-QINF-3005                                   Version No.:3.0  Version Date: Nov. 01, 2023 
 
Principal investigator’s signatures: 
I agree to:  
⚫ Be responsible for properly directing the conduct of the clinical study in the region.  
⚫ Ensure the study to be conducted in accordance with the trial protocol and standard operating 
procedures (SOPs). 
 ⚫ Ensure the participants to be fully aware of the investigational product information and other 
related responsibilities and obligations specified in this trial protocol. 
 ⚫ Ensure no changes to be made to the trial protocol without the review and written approval from 
the sponsor and Independent Ethics Committee (IEC), unless it is necessary to eliminate the 
immediate harm to the participant or to comply with the requirements of the registration authority 
(e.g., administrative aspects of the program).  
⚫ Be fully familiar with the proper use of the vaccine as described in the trial protocol and with 
other information provided by the sponsor, including but not limited to the following: the current 
investigator's brochure (IB) or the equivalent documents, as well as the IB supplementary (if 
available).  
⚫ Be familiar with and will comply with “Good Clinical Practice (GCP)”, “Guidelines for Quality 
Management of Vaccine Clinical Trials (Trial)” and all the current regulatory requirements. 
 
Name of the principal investigator:  
Signature:  
Date:   (MM/DD/YY) 

        Phase III Clinical Trial of Quadrivalent Influenza Vaccine (Split Virion) in Children Aged 6-35 Months  
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Protocol No.: PRO-QINF-3005                                                                                
                   Version No.:3.0  Version Date: Nov. 01, 2023 
 
 Protocol Synopsis 
Protocol title 
 
A Randomized, Double-Blinded, Active-Controlled Phase III Clinical 
Trial to Evaluate the Safety and Immunogenicity of Quadrivalent 
Influenza Vaccine (Split Virion) in Children Aged 6-35 Months 
Sponsor 
Sinovac Biotech Co., Ltd  
Project phase 
Phase Ⅲ 
Objective(s) 
To evaluate the safety and immunogenicity of Quadrivalent Influenza 
Vaccines. 
Study design 
Multi-center, randomized, double-blind, positive-controlled clinical trial 
Planned sample size 
3300 Participants 
Study Population 
Children in stable health aged 6-35 months. 
Investigation 
product 
Test vaccines: 
Quadrivalent Influenza Vaccine (Split Virion), inactivated, 0.25mL-dose 
and 0.5mL-dose: 
-Inactivated influenza strains (H1N1, H3N2, B Victoria and B 
Yamagata), 7.5μg per strain in 0.25mL-dose and 15μg per strain in 
0.5mL-dose 
-Sodium chloride  
-Disodium hydrogen phosphate 
-Sodium dihydrogen phosphate 
-Water for injection 
 
Control vaccines: 
Trivalent Influenza Vaccine (Split Virion), inactivated (Anflu), 
0.25mL-dose: 
-Inactivated influenza strains (H1N1, H3N2, B Victoria), 7.5μg per strain 
-Sodium chloride  
-Disodium hydrogen phosphate 
-Sodium dihydrogen phosphate 
-Water for injection 
 
Trivalent Influenza Vaccine (Split Virion), inactivated (Anflu), 
0.25mL-dose: 
-Inactivated influenza strains (H1N1, H3N2, and B Yamagata), 7.5μg per 
strain 
-Sodium chloride  
-Disodium hydrogen phosphate 
-Sodium dihydrogen phosphate 
-Water for injection 
Immunization 
Schedule 
Two-dose schedule (0,28 days) 

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Protocol No.: PRO-QINF-3005                                                                                
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Route of 
administration 
Intramuscularly: anterolateral thigh (participants aged 6-11 months); 
deltoid region (participants aged 12-35 months) 
Challenge schedule, 
if applicable 
None 
Safety endpoints 
Incidence of adverse reactions 0-28 days after each dose; 
Incidence of adverse reactions 0-7 days after each dose; 
Incidence of serious adverse events (SAEs) from the beginning of 
vaccination to 6 months after the second dose; 
Incidence of Adverse Events of Special Interest (AESIs) since the 
beginning of vaccination to 6 months after the second dose. 
Immunogenicity 
endpoints 
HI antibody seroconversion rate (SCR), seroprotection rate (SPR), 
geometric mean titer (GMT) and geometric mean fold increase (GMFI) 
28 days after the second dose 

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Protocol No.: PRO-QINF-3005                                                                                
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 Abbreviations 
AE 
Adverse Event 
AESI 
Adverse Events of Special Interest 
CDC 
Center for Disease Control and Prevention 
CRF 
Case Report Form 
EDC 
Electronic Data Capture 
FAS 
Full Analysis Set 
GCP 
Good Clinical Practice 
GMT 
Geometric Mean Titer 
GMI 
Geometric Mean Increase 
IEC 
Independent Ethics Committee 
ITT 
Intention-to-treat 
HI 
Hemagglutination inhibition test 
NMPA 
National Medical Products Administration 
PI 
Principal Investigator 
PPS 
Per Protocol Set 
SCR 
Seroconversion rate 
SPR 
Seroprotection rate 
SOP 
Standard Operation Procedure 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
SAE 
Serious Adverse Event 
SS 
Safety Set 
 

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Protocol No.: PRO-QINF-3005                                                                                
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 Summary of the clinical protocol 
The Influenza Vaccine (Split Virion), Inactivated, Quadrivalent (“QIV) developed by Sinovac 
Biotech Co., Ltd. (Sinovac), including two doses of 0.25mL and 0.5mL, is indicated for prevention 
of influenza caused by influenza viruses of H1N1, H3N2, B Victoria and B Yamagata. The 
preclinical animal trial results have shown: the vaccine has satisfactory safety and immunogenicity 
in mice, guinea pigs and rabbits. The 0.5ml-dose QIV was approved for use in individuals aged 3 
years and above on June 17, 2020. This Phase III clinical trial plans to evaluate the immunogenicity 
and safety of the 0.25ml and 0.5ml doses of QIVs developed by Sinovac in children aged 6-35 
months. This trial has been approved by the National Medical Products Administration (No.: 
2021LB00532). This clinical trial protocol is designed according to the relevant requirements of 
“Drug Registration Administration” [1], “Good Clinical Practice (GCP)”[2], “Technical Guidelines 
for Vaccine Clinical Trials”[3] and “Guidelines for Quality Management of Vaccine Clinical Trials 
(Trial)” of NMPA. 
The primary objective of this trial is to evaluate the safety and immunogenicity of 0.25ml-dose and 
0.5ml-dose QIV developed by Sinovac in children aged 6-35 months. This trial is a multi-center, 
randomized, double-blinded, and positive-controlled design. The control vaccine is Anflu®, 
two0.25mL-dose trivalent influenza virus split vaccines (TIVs, containing a B Victoria lineage or B 
Yamagata lineage） marketed by Sinovac. This trial will be conducted on children aged 6 to 35 
months with the informed consent of their guardians. A total of 3,300 participants are planned to be 
recruited and randomly assigned to 4 groups in a ratio of 2:2:1:1, namely the 0.25mL-dose QIV 
group, 0.5ml-dose QIV group, TIV-BV group, and TIV-BY group. All participants receive 2 doses 
of the test vaccine or control vaccine according to the 0, 28-day immunization schedule. 
All participants are observed for immediate reactions for 30 minutes after each dose, solicited 
systemic and local adverse events within 0-7 days, and unsolicited adverse events within 0-28 days 
after each dose. Additionally, monitoring of serious adverse events (SAEs) and adverse events of 
special interest (AESIs) is conducted from the first dose administration to 6 months after the second 
vaccination to evaluate the safety. Venous blood samples are collected from all participants before 
immunization and 28 days after the second immunization for hemagglutination inhibition (HI) 
antibody detection to assess the immunogenicity of the vaccine. 
This clinical protocol will be independently undertaken by investigators after obtaining approval 
from the Ethics Committee. Monitors designated by the sponsor will supervise the standardization 
of the entire study process to ensure the trial is conducted safely and in compliance with 
regulations. 

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Protocol No.: PRO-QINF-3005                                                                                
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Content 
PROTOCOL SYNOPSIS .......................................................................................................................................... 3 
ABBREVIATIONS .................................................................................................................................................... 5 
SUMMARY OF THE CLINICAL PROTOCOL ...................................................................................................... 6 
CONTENT ................................................................................................................................................................ 7 
1. 
INTRODUCTION ......................................................................................................................................... 9 
2. 
BACKGROUND AND RATIONALE ........................................................................................................... 9 
2.1 
ETIOLOGY ................................................................................................................................................... 9 
2.2 
EPIDEMIOLOGY ...........................................................................................................................................10 
2.3 
RESEARCH, DEVELOPMENT OF QUADRIVALENT INFLUENZA VACCINES .......................................................... 11 
2.4 
STUDY RATIONALE ......................................................................................................................................12 
3. 
PRECLINICAL STUDY RESULTS ............................................................................................................13 
4. 
PRELIMINARY CLINICAL STUDIES ......................................................................................................13 
5. 
PRODUCT CHARACTERISTICS ..............................................................................................................13 
5.1 
PREPARATION PROCESS AND FORMULATION OF THE TEST VACCINE ...............................................................13 
5.2 
STABILITY OF THE VACCINE .........................................................................................................................13 
5.3 
CONTROL VACCINES....................................................................................................................................14 
5.4 
STORAGE AND TRANSPORTATION OF THE VACCINE ........................................................................................14 
5.5 
VACCINATION ROUTE AND SCHEDULE ..........................................................................................................14 
5.6 
INFORMATION ON THE TEST VACCINE ...........................................................................................................14 
6. 
STUDY OBJECTIVES.................................................................................................................................15 
6.1 
PRIMARY OBJECTIVE ...................................................................................................................................15 
6.2 
SECONDARY OBJECTIVE ...............................................................................................................................15 
7. 
STUDY DESIGN ..........................................................................................................................................15 
7.1 
DESIGN.......................................................................................................................................................15 
7.2 
STUDY ENDPOINT ........................................................................................................................................17 
7.3 
ESTIMAND ..................................................................................................................................................18 
7.4 
STUDY PLAN ...............................................................................................................................................20 
7.5 
RANDOMIZATION AND BLINDING ..................................................................................................................21 
7.6 
CLINICAL TRIAL FLOWCHART ......................................................................................................................23 
7.7 
STUDY DURATION........................................................................................................................................24 
7.8 
SUSPENSION AND EARLY TERMINATION ........................................................................................................24 
7.9 
PROTOCOL DEVIATION .................................................................................................................................24 
8. 
PARTICIPANTS ..........................................................................................................................................25 
8.1 
INCLUSION CRITERIA ...................................................................................................................................25 
8.2 
EXCLUSION CRITERIA FOR THE FIRST DOSE OF VACCINATION .........................................................................25 
8.3 
EXCLUSION CRITERIA FOR THE SECOND DOSE OF VACCINATION......................................................................26 
8.4 
CRITERIA FOR WITHDRAWAL AND TERMINATION ...........................................................................................26 

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Protocol No.: PRO-QINF-3005                                                                                
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9. 
STUDY PROCEDURE.................................................................................................................................27 
9.1 
SCHEDULE OF ACTIVITIES ............................................................................................................................27 
9.2 
ENROLLMENT AND INFORMED CONSENT .......................................................................................................28 
9.3 
SCREENING AND RANDOMIZATION ...............................................................................................................28 
9.4 
VACCINATION .............................................................................................................................................28 
9.5 
SAFETY FOLLOW-UP OBSERVATION ...............................................................................................................28 
9.6 
BLOOD SAMPLE COLLECTION .......................................................................................................................29 
9.7 
SAFETY EVALUATION ..................................................................................................................................30 
9.8 
CONCOMITANT MEDICATIONS AND VACCINES ................................................................................................35 
9.9 
IMMUNOGENICITY EVALUATION ...................................................................................................................36 
9.10 
DATA MANAGEMENT ...................................................................................................................................36 
9.11 
STATISTICAL ANALYSIS ...............................................................................................................................38 
10. 
MONITORING OF THE CLINICAL TRIALS...........................................................................................38 
10.1 
RESPONSIBILITIES OF THE SPONSOR .............................................................................................................38 
10.2 
RESPONSIBILITIES OF THE INVESTIGATORS....................................................................................................39 
10.3 
PERSONNEL TRAINING .................................................................................................................................39 
10.4 
PARTICIPANT COMPLIANCE ASSURANCE ........................................................................................................39 
10.5 
INVESTIGATIONAL VACCINE MANAGEMENT...................................................................................................39 
10.6 
CLINICAL TRIAL SAMPLE MANAGEMENT .......................................................................................................40 
10.7 
CLINICAL TRIAL DATA STORAGE ...................................................................................................................40 
10.8 
COMPLETION CRITERIA FOR THE CLINICAL TRIALS ........................................................................................40 
11. 
ETHICAL APPROVAL ................................................................................................................................41 
11.1 
REVIEW AND APPROVAL ...............................................................................................................................41 
11.2 
IMPLEMENTATION OF ON-SITE SUPERVISION ..................................................................................................41 
11.3 
CONFIDENTIALITY ......................................................................................................................................42 
12. 
REVISION OF CLINICAL TRIAL PROTOCOL ......................................................................................42 
13. 
DATA DISCLOSURE AND PUBLICATION ..............................................................................................42 
14. 
REFERENCE ...............................................................................................................................................42 
 

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Protocol No.: PRO-QINF-3005                                                                                
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1. Introduction 
The Influenza Vaccine (Split Virion), Inactivated, Quadrivalent (QIV) developed by Sinovac 
Biotech Co., Ltd. (Sinovac), including two doses of 0.25mL and 0.5mL, is indicated for prevention 
of influenza caused by influenza viruses of H1N1, H3N2, B Victoria and B Yamagata. The 
preclinical animal trial results have shown: the vaccine has satisfactory safety and immunogenicity 
in mice, guinea pigs and rabbits. The 0.5ml-dose QIV was approved for use in individuals aged 3 
years and above on June 17, 2020. This Phase III clinical trial plans to evaluate the immunogenicity 
and safety of the 0.25ml and 0.5ml doses of QIVs developed by Sinovac in children aged 6-35 
months. This trial has been approved by the National Medical Products Administration (No.: 
2021LB00532). This clinical trial protocol is designed according to the relevant requirements of 
“Drug Registration Administration” [1], “Good Clinical Practice (GCP)” [2], “Technical Guidelines 
for Vaccine Clinical Trials” [3] and “Guidelines for Quality Management of Vaccine Clinical Trials 
(Trial)” of NMPA. 
2. Background and rationale 
Influenza (flu) is an acute respiratory infectious disease caused by influenza viruses, which can 
cause outbreaks and epidemics worldwide. The disease burden imposed by influenza varies across 
different regions and populations. Globally, approximately 5%-10% of adults and 20%-30% of 
children suffer from seasonal influenza each year, leading to 3 to 5 million severe cases and 250,000 
to 500,000 deaths annually, posing a serious threat to public health. The main clinical 
manifestations include fever, headache, myalgia, fatigue, rhinitis, sore throat, and cough. Over the 
past three centuries, influenza has been one of the major infectious diseases. At present, the 
transmission routes of influenza viruses and the continuous mutation of the virus remain the main 
obstacles to the prevention and control of influenza. 
2.1 
Etiology 
Influenza viruses belong to the Orthomyxoviridae family, and are single-stranded, negative-sense, 
segmented RNA viruses. Based on their nucleoprotein and matrix protein, influenza viruses are 
classified into four types: A, B, C, and D. Influenza A viruses can be further divided into multiple 
subtypes according to the protein structure and genetic characteristics of hemagglutinin (HA) and 
neuraminidase (NA) on the viral surface. Currently, 18 HA subtypes (H1-H18) and 11 NA subtypes 
(N1-N11) have been identified [5]. In addition to infecting humans, influenza A viruses are widely 
present in animals, such as poultry, pigs, horses, seals, whales, and minks. Influenza B viruses are 
divided into Victoria lineage and Yamagata lineage, which can circulate among the human 
population, and recent data have shown that seals can also be infected. Influenza C viruses infect 
humans, dogs, and pigs, and only cause sporadic cases of upper respiratory tract infections [6]. 
Influenza D viruses mainly infect pigs, cattle, etc., and no human infections have been found so far 
[7-9]. At present, the viruses causing seasonal influenza epidemics are H1N1 and H3N2 subtypes of 
influenza A, as well as Victoria and Yamagata lineages of influenza B. 
 

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Protocol No.: PRO-QINF-3005                                                                                
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2.2 
Epidemiology 
Patients with influenza and asymptomatic carriers are the main sources of infection for seasonal 
influenza. The virus is primarily transmitted through droplets from their respiratory secretions, and 
can also be spread via direct or indirect contact with the mucous membranes of the mouth, nose, 
eyes, etc. The common incubation period is 1-4 days (with an average of 2 days), and infectivity 
persists from the end of the incubation period to the acute phase of the illness. Generally, infected 
individuals can shed the virus 24-48 hours before the onset of clinical symptoms; the amount of 
virus shedding increases significantly 0.5-1 day after infection and reaches a peak within 24 hours 
of the onset of illness [10]. Adults and older children usually continue to shed the virus for 3-8 days 
(average 5 days). Younger children shed the same amount of virus as adults when they fall ill, but 
the decrease in virus shedding is slower and the duration of shedding is longer. Compared with 
adults, prolonged virus shedding (1-3 weeks) is common in children. 
In temperate regions, influenza exhibits seasonal outbreaks and high incidence during winter and 
spring each year. In 2013, a study on the seasonality of influenza in different regions of China [11] 
showed that the annual periodicity of influenza A in China strengthens with increasing latitude, 
presenting diverse spatial patterns and seasonal characteristics: in northern provinces north of 33°N, 
it shows a winter epidemic pattern with a single annual peak in January to February; in the 
southernmost provinces south of 27°N, there is a single annual peak in April to June; in the 
mid-latitude regions, there are two periodic peaks in January to February and June to August. While 
influenza B shows a single winter peak in most areas of China. In 2018, a systematic analysis study 
was conducted on the epidemiological characteristics of influenza B in China from 2005 to 2016 [12]. 
Overall, the epidemic intensity of influenza B in China is lower than that of influenza A; however, 
in some regions and years, the epidemic intensity of influenza B is higher than that of influenza A. 
Additionally, the B/Yamagata lineage and B/Victoria lineage alternately dominate, with epidemics 
mainly occurring in winter and spring, and the epidemic intensity of different lineages varies across 
years. 
During annual influenza seasons, the incidence of influenza in children is approximately 20-30%, 
and in some high-prevalence seasons, the annual infection rate in children can reach around 50% [13, 
14]. A review study on influenza incidence (including both symptomatic and asymptomatic 
infections) [15] indicated that the influenza incidence rate in children under 18 years old is 
approximately 22.5% (95% CI: 9.0-46.0%), while that in adults is about 10.7% (95% CI: 
4.5-23.2%). A study on influenza infection and incidence rates in Beijing during the 2017-2018 
season showed that the 0-4 years age group and 5-14 years age group had the highest incidence 
rates, at 33.0% (95% CI: 26.4-43.1%) and 21.7% (95% CI: 17.4-28.4%), respectively [16]. A study in 
Suzhou reported that the consultation rate for influenza-like illness (ILI) caused by confirmed 
influenza in children under 5 years old during the 2011-2017 seasons was 6.4 per 100 person-years, 
with the highest rate in the 2011-2012 season (20.5 per 100 person-years) and the lowest in the 
2012-2013 season (2.4 per 100 person-years) [17]. 
Children under 5 years old are at a high risk of developing severe illness after influenza infection. A 
systematic review and modeling study on the burden of influenza-related respiratory infections in 
children under 5 years old worldwide [18] indicated that in 2018, approximately 109.5 million 
(uncertainty range [UR]: 63.1-190.6 million) children under 5 years old globally were infected with 
influenza viruses, 10.1 million (UR: 6.8-15.1 million) developed influenza-related acute lower 

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Protocol No.: PRO-QINF-3005                                                                                
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respiratory infections (ALRI), 870,000 (UR: 543,000-1.415 million) were hospitalized due to 
influenza-related ALRI, 15,300 (UR: 5,800-43,800) in-hospital deaths occurred among 
influenza-related ALRI, and 34,800 (UR: 13,200-97,200) deaths were attributed to influenza-related 
ALRI cases. A population-based study in Jingzhou City, Hubei Province, found that 69% of 
hospitalized cases with severe acute respiratory infection (SARI) caused by influenza were children 
under 5 years old, with the influenza-related SARI hospitalization rate in this age group reaching 
2,021-2,349 per 100,000 person-years, and the highest rate among infants aged 6-11 months 
(3,603-3,805 per 100,000 person-years) [19]. A study in Suzhou on the confirmed influenza-related 
SARI hospitalization rate in children under 5 years old during the 2011-2016 seasons [20] showed 
that the rate ranged from 4 cases per 1,000 people (95% CI: 2-5 cases per 1,000 people) in the 
2012-2013 season to 16 cases per 1,000 people (95% CI: 14-19 cases per 1,000 people) in the 
2011-2012 season. Influenza infection in children can lead to death. Children with underlying 
diseases have a significantly higher risk of death than healthy children, but nearly half of the fatal 
cases occur in healthy children [21]. A modeling study on global influenza-related deaths estimated 
that approximately 9,243-105,690 children under 5 years old die annually from influenza-related 
respiratory diseases in the 92 included countries [22]. 
2.3 
Research, Development of Quadrivalent Influenza Vaccines 
Before 1976, influenza vaccines in the United States contained only two virus strains. The 
components of seasonal influenza vaccines included three types of virus strains recommended by 
the World Health Organization (WHO) or the U.S. Centers for Disease Control and Prevention 
(CDC) since 1976. Since the 1980s, the global epidemic has been characterized by the concurrent 
circulation and co-transmission of two B-type virus lineages, Yamagata and Victoria, with poor 
cross-protection between them. Therefore, in recent years, most domestic and foreign vaccine 
manufacturers have recognized the necessity of developing quadrivalent influenza vaccines. 
Currently, some manufacturers have obtained approval for their quadrivalent influenza vaccines to 
be marketed, some are conducting clinical studies on quadrivalent influenza vaccines. 
In December 2012, U.S. FDA approved GlaxoSmithKline (GSK)'s QIV (Fluarix Quadrivalent), 
which was also the first QIV in history, available in pre-filled syringes. On August 16, 2013, GSK's 
second quadrivalent influenza vaccine, FluLaval Quadrivalent, was also approved by the U.S. FDA 
for active immunization in individuals aged 6 months and older. Both vaccines are used to prevent 
influenza caused by seasonal influenza A and B strains. On June 10, 2013, Sanofi Pasteur 
announced that the U.S. FDA had approved its QIV (Fluzone® Quadrivalent) for active 
immunization in individuals aged 6 months and older to prevent influenza caused by seasonal 
influenza A strains and B strains. In August 2016, the U.S. FDA approved Seqirus' quadrivalent 
influenza vaccine Afluria® Quadrivalent for the first time, for use in adults aged 18 years and older 
to prevent influenza caused by seasonal influenza A and B strains and approved the vaccine for use 
in individuals aged 6 months and older in October 2018. 
For the 2022-2023 influenza season, the U.S. Center for Disease Control and Prevention (CDC) 
recommends quadrivalent influenza vaccines for children aged 6-35 months as shown in Table 1. 
 

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Protocol No.: PRO-QINF-3005                                                                                
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Table 1 Quadrivalent Influenza Vaccines Recommended by the U.S. CDC for Children Aged 
6-35 Months in the 2022-23 Influenza Season 
Trade Name (Manufacturer) 
Doses 
Afluria® Quadrivalent (Seqirus) 
0.25 mL (7.5μɡ) and 0.5ml（15μɡ） 
Fluarix® Quadrivalent (GlaxoSmithKline) 
0.5 mL (15μɡ) 
FluLaval® Quadrivalent (GlaxoSmithKline) 
0.5 mL (15μɡ) 
Fluzone® Quadrivalent (Sanofi Pasteur) 
0.25 mL (7.5μɡ) or 0.5 mL (15μɡ) 
Flucelvax® Quadrivalent (Seqirus), cell 
substrate 
0.5 mL (15μɡ) 
 
Since 2013, domestic vaccine manufacturers have recognized the necessity of developing 
quadrivalent influenza vaccines. At present, several domestic manufactures have launched 
quadrivalent influenza vaccines on the market, but only three of them are intended for children aged 
6-35 months. These include the quadrivalent influenza vaccine from Hualan Biological Engineering, 
Inc., Shanghai Institute of Biological Products Co., Ltd. and Shenzhen Sanofi Pasteur Biological 
Products Co., Ltd.  
2.4 
Study rationale 
Immunization Schedule: The target population of this clinical trial is children aged 6-35 months, 
with an immunization schedule of 2 doses (28 days apart), consistent with the approved trivalent or 
quadrivalent influenza vaccines currently on the market. 
Vaccination Dose: The vaccination doses in this clinical trial include the 0.25ml dose (containing 
7.5μg of hemagglutinin for each strain) and the 0.5ml dose (containing 15μg of hemagglutinin for 
each strain). Among them, the 0.25ml influenza vaccine has been used in the 6-35 months age 
group for over 30 years. Initially, half-dose antigen influenza vaccines were developed to reduce the 
risk of fever convulsions that might be caused by whole-virus influenza vaccines [23]. However, 
several recent studies have shown that children under 3 years old can receive full-dose vaccines to 
enhance immunogenicity without increasing the severity or incidence of fever or other adverse 
reactions [24-26]. In the United States, the 0.5ml dose of QIV was first approved for use in children 
aged 6-35 months in 2016. Currently, multiple domestic manufacturers are also conducting clinical 
trials on both 0.25ml and 0.5ml doses vaccines in this population. 
Control Selection: In this clinical trial, two 0.25ml trivalent influenza vaccines (TIVs, Anflu®) 
marketed by Sinovac were selected as the control vaccines. Anflu® has been marketed and used in 
China for 20 years, with previous study results showing good protective efficacy, immunogenicity, 
and safety. The immunogenicity results would be comparable due to the same strains and 
manufacturing process between test and control vaccines. Additionally, relevant studies have shown 
that some indicators of immune responses to the two B serotypes in quadrivalent influenza vaccines 
may be lower than those in trivalent influenza vaccines. For example, in a clinical study of 
quadrivalent influenza vaccines in the 6-35 months age group, the geometric mean titers (GMT) of 
HI antibodies against the BV serotype at 28 days after full immunization were 64.0 in the 0.25ml 
quadrivalent influenza vaccine group and 91.3 in the trivalent influenza vaccine (containing BV) 
group; the GMTs of HI antibodies against the BY serotype were 96.6 in the 0.25ml quadrivalent 
influenza vaccine group and 106 in the trivalent influenza vaccine (containing BY) group [27]. 

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Protocol No.: PRO-QINF-3005                                                                                
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Therefore, two trivalent influenza vaccines were selected as controls in this study. Furthermore, 
since domestic marketed influenza vaccines currently lack data on protective efficacy, Sinovac will 
conduct post-marketing protective efficacy studies in a timely manner to accumulate data on the 
effectiveness of seasonal influenza vaccines in China. 
3. Preclinical study results 
See in Investigator's Brochure (IB). 
4. Preliminary Clinical Studies 
See in Investigator's Brochure (IB). 
5. Product Characteristics 
5.1 
Preparation Process and Formulation of the Test Vaccine 
The quadrivalent influenza virus split vaccine is prepared by inoculating the influenza A and B virus 
strains recommended by the World Health Organization (WHO) for the 2023-2024 Northern 
Hemisphere influenza season and approved by the national food and drug regulatory authority into 
chicken embryos, respectively. The vaccine is manufactured through virus culture, harvest of virus 
liquid, virus inactivation, purification, and splitting. The test vaccine is a clear liquid, packaged in 
pre-filled syringes, with doses of 0.25ml or 0.5ml per syringe. 
The strains contained in the test vaccine (0.25ml or 0.5ml) are the strains recommended for the 
2023-2024 Northern Hemisphere influenza season, as follows: 
A/Victoria/4897/2022 (H1N1) pdm09-like virus ……………………………7.5μg or 15μg 
hemagglutinin 
A/Darwin/9/2021 
(H3N2)-like 
virus 
………………………………………7.5μg 
or 
15μg 
hemagglutinin 
B/Austria/1359417/2021 
(B/Victoria 
lineage) 
……………………………7.5μg 
or 
15μg 
hemagglutinin 
B/Phuket/3073/2013 
(B/Yamagata 
lineage) 
………………………………7.5μg 
or 
15μg 
hemagglutinin 
Inactive ingredients include sodium chloride, sodium dihydrogen phosphate, disodium hydrogen 
phosphate, and water for injection. The test vaccine is prepared by Sinovac Biotech Co., Ltd., and 
has been inspected by the National Institutes for Food and Drug Control, with all test results 
meeting the requirements of the Manufacturing and Inspection Procedures for Quadrivalent 
Influenza Virus Split Vaccine (draft) or Manufacturing and Inspection Procedures for Quadrivalent 
Influenza Virus Split Vaccine (approval number: 2020S00335). 
5.2 
Stability of the Vaccine 
When stored at 2-8°C for 12 months, all test results of the test vaccine meet the quality standards. 
When stored at 25°C for 14 days, all test results meet the quality standards; when stored at 25°C for 
21 days, the hemagglutinin content fails to meet the quality standards. 

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Protocol No.: PRO-QINF-3005                                                                                
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When stored at 37°C for 3 days, all test results meet the quality standards; when stored at 37°C for 
7 days, the hemagglutinin content fails to meet the quality standards. 
Based on the stability test results at 2-8°C and with reference to the stability results at 25°C and 
37°C, the validity period of the test vaccine is set as 1 year. 
5.3 
Control Vaccines 
The control vaccines (Anflu) are trivalent influenza virus split vaccines prepared with the strains 
recommended by WHO for the 2023-2024 Northern Hemisphere influenza season. Control Vaccine 
1 is the marketed Anflu for the 2023-2024 influenza season, containing 7.5μg each of H1N1, H3N2, 
and BV antigens. Control Vaccine 2 contains 7.5μg each of H1N1, H3N2, and BY antigens. The 
sources of antigen strains for each type in the control vaccines are consistent with those 
corresponding to the quadrivalent influenza vaccine. The control vaccines are prepared by Sinovac 
Biotech Co., Ltd., packaged in pre-filled syringes, with a dose of 0.25ml per syringe, and have been 
inspected by the National Institutes for Food and Drug Control, meeting the requirements of the 
Manufacturing and Inspection Procedures for Influenza Virus Split Vaccine. 
5.4 
Storage and Transportation of the Vaccine 
The vaccine should be stored and transported at 2-8°C in the dark; freezing is strictly prohibited. 
5.5 
Vaccination Route and Schedule 
Eligible participants will receive 2 doses of the 0.25ml or 0.5ml test vaccine or control vaccine 
according to the 0, 28-day schedule. Participants aged 6-11 months (before their first birthday) will 
receive intramuscular injection in the anterolateral thigh, and those aged 12-35 months will receive 
intramuscular injection in the deltoid muscle of the upper arm. 
5.6 
Information on the Test Vaccine 
Information on the vaccine used in the clinical trial is shown in the table below: 
Table 2 Information on Vaccines Used in Clinical Trial 
Group 
Vaccine Name 
Manufactur
er 
Dosage 
Batch No. 
Expiry Date 
Test 
Group 1 
Quadrivalent 
Influenza Virus Split 
Vaccine 
Sinovac 
7.5µg per 
strain / 0.25ml 
LA20230502T 
2024.05.2
3 
Test 
Group 2 
Quadrivalent 
Influenza Virus Split 
Vaccine 
Sinovac 
15µg per strain 
/ 0.5ml 
LA202305002 
2024.05.2
1 
Control 
Group 1 
Anflu (containing B 
Victoria) 
Sinovac 
7.5µg per 
strain / 0.25ml 
CA202305001 
2024.05.2
1 
Control 
Group 2 
Anflu (containing B 
Yamagata) 
Sinovac 
7.5µg per 
strain / 0.25ml 
CA20230507T 
2024.05.2
3 
 

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Protocol No.: PRO-QINF-3005                                                                                
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6. Study Objectives 
6.1 
Primary objective 
- 
To evaluate the non-inferiority of immunogenicity in participants aged 6-35 months after 2 
doses of 0.5mL-dose QIV compared with two TIVs (including BV or BY) for the shared strains, in 
terms of seroconversion rate (SCR) and Geometric mean titer (GMT) for HI antibody;  
- 
To evaluate the non-inferiority of immunogenicity in participants aged 6-35 months after 2 
doses of 0.25mL-dosen QIV compared with two TIVs (including BV or BY) for the shared strains, 
in terms of SCR and GMT for HI antibody;  
- 
To evaluate the absolute criteria of HI antibody SCR and seroprotection rate (SPR) for each 
strain in participants aged 6-35 months after two doses of 0.25mL-dose or 0.5mL-dose QIVs. 
6.2 
Secondary objective 
- 
To evaluate the non-inferiority of immunogenicity in participants aged 6-35 months after 2 
doses of 0.5mL-dose QIV compared with 0.25mL-dose QIV for each strain, in terms of 
seroconversion rate and GMT of HI antibody;  
- 
To evaluate the superiority of immunogenicity in participants aged 6-35 months after 2 doses of 
0.25mL-dose or 0.5mL-dose QIVs compared with two TIVs (including BV or BY) for the unique 
strain, in terms of seroconversion rate and GMT of HI antibody;  
- 
To evaluate the immunogenicity in participants aged 6-35 months after vaccination of 2 doses 
of 0.25mL-dose or 0.5mL-dose QIVs; 
- 
To evaluate the safety of 0.25mL-dose or 0.5mL-dose QIVs in participants aged 6-35 months. 
7. Study design 
7.1 
Design 
7.1.1 Overall study design 
A multi-centered, randomized, blinded (double-blinded), and controlled trial design. 
7.1.2 Sample size calculation 
This trial requires the test group: ① the non-inferiority comparison with the control groups is 
established and the next statistical test is carried out; ② when the absolute criteria of SCR and 
SPR are achieved, the trial can be considered as successful and a positive conclusion can be drawn 
for the test group. In this trial, when evaluating between the test group 1 (0.25-mL QIV) and test 
group 2 (0.5mL-QIV), the strategy of sequential test is adopted. First, test group 2 is evaluated. If 
the positive conclusion of test group 2 is established, test group 1 is further evaluated. Therefore, 
class Ⅰ error correction is no longer carried out. The sample size of phase Ⅲ clinical trials is 
estimated first by non-inferiority design, namely the QIV group is non-inferior to the TIV group. 
The primary endpoints of this study include two indicators: SCR and GMT. Only when the SCR 
and GMT of four serotypes in test group are non-inferior to the control vaccine, the investigational 
vaccine is considered to be non-inferior to the control vaccine. The total power is 80%, the type Ⅱ 

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Protocol No.: PRO-QINF-3005                                                                                
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error is 0.2. Based on the different sample size requirements of the two indicators, the type Ⅱ error 
is allocated, with 0.16 for seroconversion rate comparison and 0.04 for GMT comparison.  
(1) Calculation of sample size with the SCR as the indicator:  
According to the results of the previous Anflu phase Ⅳ clinical trial and other literature, the SCR of 
the types contained in the vaccine 28 days after vaccination is over 65%, which is used as the 
reference proportion to estimate the sample size. The test level is taken as one-sided α=0.025, the 
power of non-inferiority comparison for the seroconversion rate of a serotype is taken as 
1-β1/4=1-0.16/4=96%, and the non-inferiority threshold Δ is taken as -10%. When comparing the 
non-inferiority of BY or BV strain, NT:NC=2:1, and PASS software is used to calculate the sample 
size, the test group needs 914 samples and the control group needs 457 samples. When the 
non-inferiority test of H1N1 or H3N2 strain is carried out, two control groups are pooled. The 
sample size ratio of the test group and the pooled control group is 1:1, and the test group and the 
pooled control group need 625 participants.  
(2) Calculation of sample size with the GMT as the indicator:  
Using the antibody GMT 28 days after vaccination as the outcome measure, the non-inferiority 
margin is ≥2/3 of the 95%CI lower limit of GMT ratio between the test group and the control group, 
and the non-inferiority margin after logarithmic conversion is Δ=-0.176. The test level is taken as 
one-sided α=0.025, and the power of a certain serotype GMT for non-inferiority comparison is 
taken as 1-β2/4=1-0.04/4=99%, and the standard deviation after logarithmic transformation is taken 
as σ =0.7 with reference to the previous research results. When comparing the non-inferiority of BY 
or BV, NT:NC=2:1, and PASS software is used to calculate the sample size, the test group needs 
874 samples and the control group needs 437 samples. When the non-inferiority test of H1N1 or 
H3N2 type is carried out, two control groups are pooled. The sample size ratio of the test group and 
the pooled control group is 1:1, and the test group and the pooled control group need 582 
participants each.  
When the SCR and GMT of the test group reach the hypothesis of non-inferiority, the absolute 
criteria of the SCR and seroprotection rate (SPR) of the test group are further hypothesized for test. 
The trial requires that the SCR and SPR of the four strains of immune antibodies reach the absolute 
criteria, and the total power of the trial is 80%, so the power of each test is 1- (0.2/8)=0.975. 
(3) Calculation of sample size with the absolute criteria of SCR:  
Assuming that the SCR after vaccination is 65%, the test level is one-sided α=0.025, the lower limit 
of the confidence interval of the seroconversion rate should be greater than 30%, and the power of 
each test is 97.5%. The sample size is calculated by PASS software, and the test group needs 28 
samples. 
(4) Calculation of sample size with the absolute criteria of SPR:  
Assuming that the seroconversion rate after vaccination is 75%, the test level is one-sided α=0.025, 
the lower limit of the confidence interval of the SPR should be greater than 60%, and the power of 
each test is 97.5%. The sample size is calculated by PASS software, and the test group needs 146 
samples. 
In consideration of the above the maximum sample size and the dropout rate of about 17%, the 
sample size of each test group is 1,100, and the sample size of each control group is 550, with a 
total sample size of 3,300. 

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Protocol No.: PRO-QINF-3005                                                                                
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7.2 
Study endpoint 
Co-primary endpoint and evaluation criteria: 
(1) The HI antibody GMTs and SCRs for each of the four strains in QIV groups were inferior to 
those of control groups at 28 days after vaccination in total populations. The non-inferiority 
criteria are as follows: 
- 
GMTs: Non-inferiority of GMTs was demonstrated if the lower limit of the two-sided 95% 
confidence interval (CI) for adjusted GMT ratio (test group/control group) ≥ 2/3 for each of the 
four strains. 
- 
SCRs: The percentages of participants with either a pre-vaccination titer <1:10 and a 
post-vaccination titer ≥1:40, or a pre-vaccination titer ≥ 10 and a ≥ 4-fold increase in 
post-vaccination titer at 28 days after vaccination. Non-inferiority for SCR was demonstrated if 
the lower limit of the two-sided 95% CI for SCR difference (test group-control group) was 
≥-10% for each of the 4 strains. 
(2) The SCRs and SPRs should meet the absolute criteria in total populations.  
- 
Absolute criteria of SCR and SPR: the lower limit of the two-sided 95%CI for SCR was ≥30%; 
the lower limit of the two-sided 95%CI for SPR was ≥60%. 
Second endpoint and evaluation criteria: 
➢ Immunogenicity endpoint 
(1) The HI antibody GMTs and SCRs for the unique B strain in QIV groups were superior to those 
of control groups at 28 days after vaccination in total populations. The criteria for superiority 
were as follows: 
- 
The lower limit of the two-sided 95%CI for adjusted GMT ratio (test group/control group) 
≥1.5; 
- 
The lower limit of the two-side 95% CI for SCR difference (test group-control group) was ≥ 
10%. 
(2) The HI antibody GMTs and SCRs for each of the four strains in 0.5mL-dose QIV group were 
inferior to those of 0.25-mL-dose QIV at 28 days after vaccination in total populations. The 
non-inferiority criteria were consistent with the co-primary endpoints.  
(3) The HI antibody GMIs of each strain at 28 days after second vaccination in total population;  
(4) The HI antibody SCRs, SPRs, GMTs and geometric mean fold increasing (GMFIs) of 
0.5mL-dose QIV and 0.25mL-dose QIV in susceptible population (HI antibody titers ＜1:10). 
The non-inferiority, superiority and absolute criteria refer to the total population. 
➢ Safety endpoint 
(1) Incidence of adverse reactions in 0-28 days after each dose of QIVs;  
(2) Incidence of adverse reactions in 0-7 days after each dose of QIVs;  
(3) Incidence of SAE from the beginning of the first dose to 6 months after second dose;  
(4) Incidence of AESI from the beginning of first dose to 6 months after second dose. 

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Protocol No.: PRO-QINF-3005                                                                                
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7.3 
Estimand 
7.3.1 Primary Estimand 
Table 3 Primary Estimand 
 
Primary Estimand 
Population 
The target population involves all participants aged 6 to 35 months who have completed 
two doses of vaccination. 
Variable 
(1) Whether the H1N1 and H3N2 HI antibodies are seroconverted in the test group (0.5mL 
or  
0.25mL) and the pooled TIV group 28 days after the second dose. 
(2) Whether the BV HI antibody is seroconverted in the test group (0.5mL or 0.25mL) and 
the TIV-BV groups 28 days after the second dose. 
(3) Whether the BY HI antibody is seroconverted in the test group (0.5mL or 0.25mL) and 
the TIV-BY group 28 days after the second dose. 
(4) H1N1 and H3N2 HI antibody titers of the test group (0.5mL or 0.25mL) and the pooled 
TIV group 28 days after the second dose. 
(5) BV HI antibody titers of the test group (0.5mL or 0.25mL) and the TIV-BV groups 28 
days after the second dose. 
(6) BY HI antibody titers of the test group (0.5mL or 0.25mL) and the TIV-BY group 28 
days after the second dose. 
(7) Whether the H1N1, H3N2, BV, and BY HI antibody titer reach the protective antibody 
level in the test group (0.5mL or 0.25mL) 28 days after the second dose.  
Treatments 
Subjects received two doses of the test vaccine or the control vaccine according to the 
0,28-day schedule. 
Intercurrent  
Events and  
Treatment  
Strategies 
The definition is shown in Table 4. 
Population-level 
Summary 
(1) Difference between the SCRs of H1N1 and H3N2 HI antibodies of the test group 
(0.5mL or 0.25mL) and the pooled TIV group 28 days after the second dose. 
(2) Difference between the SCRs of BV serum HI antibodies of the test group (0.5mL or 
0.25mL) and the TIV-BV group 28 days after the second dose. 
(3) Difference between the SCRs of BY HI antibodies of the test group (0.5mL or 0.25mL) 
and the TIV-BY group 28 days after the second dose vaccination. 
(4) GMT ratios of H1N1 and H3N2 HI antibodies of the test group (0.5mL or 0.25mL)  
and the pooled TIV group 28 days after the second dose 
(5) GMT ratios of BV serum HI antibodies of the test group (0.5mL or 0.25mL) and the  
trivalent control group (including BV) after 28 days of full-course vaccination. 
(6) GMT ratios of BY serum HI antibodies of the test group (0.5mL or 0.25mL) and the  
trivalent control group (including BY) after 28 days of full-course vaccination. 
(7) Seroprotection rates (SPRs) of H1N1, H3N2, BV, and BY HI antibody in the test group 
(0.5mL or 0.25mL) after 28 days after the second dose. 
 

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Protocol No.: PRO-QINF-3005                                                                                
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Table 4 Intercurrent Events and Treatment Strategies of Primary Estimand 
Intercurrent Event 
Treatment Strategy 
Remarks 
Use of concomitant medication/vaccines 
within 28 days of full-course vaccination 
that 
affect 
the 
immunogenicity 
evaluation 
Hypothetical strategy 
Treating the post-vaccination antibody data 
after 
the 
use 
of 
concomitant 
medication/vaccines as missing data 
The interference of 
confounding 
factors 
is  
eliminated 
The blood collection after 28-day 
full-course vaccination exceeds the 
acceptable 
time 
window 
for 
immunogenicity evaluation 
Hypothetical strategy 
Treating the post-vaccination antibody data 
when the time window is exceeded as 
missing data 
Failure 
to 
reflect 
antibody results at 
planned time nodes 
Early discontinuation of treatment due to 
loss of visits, withdrawal of informed 
consent, etc., and failure to complete the 
full-course vaccination 
Primary strategy 
Excluding the corresponding population 
evaluated for 
the 
primary 
estimation 
objectives 
Not 
the 
main 
population evaluated 
for 
the 
primary 
estimation objectives 
7.3.2 Secondary Estimand 1 
Table 5 Secondary Estimand 1 
 
Secondary Estimand 1 
Population 
The target population involves all participants aged 6 to 35 months who have completed 
two doses of vaccination. 
Variable 
(1) Whether the H1N1, H3N2, BV, and BY HI antibodies are seroconverted in both the test 
group 2 (0.5mL) and the test group 1 (0.25mL) 28 days after the second dose. 
(2) H1N1, H3N2, BV, and BY serum HI antibody titers of the test group 2 (0.5mL) and the 
test  
group 1 (0.25mL) 28 days after the second dose. 
Treatments 
As the same as the primary estimand 
Intercurrent  
Events and  
Treatment  
Strategies 
As the same as the primary estimand 
Population-level 
Summary 
(1) Difference between the SCRs of H1N1, H3N2, BV, and BY serum HI antibodies of the 
test group (0.5mL) and the test group (0.25mL) 28 days after the second dose. 
(2) GMT ratios of H1N1, H3N2, BV, and BY serum HI antibodies between the test group 
(0.5mL) and the test group (0.25mL) 28 days after the second dose. 
7.3.3 Secondary Estimand 2 
Table 6 Secondary Estimand 2 
 
Secondary Estimand 2 
Population 
The target population involves all participants aged 6 to 35 months who have completed two 
doses of vaccination. 
Variable 
(1) Whether the BV HI antibody is seroconverted in the test group (0.5mL or 0.25mL) and 
the TIV-BY group 28 days after the second dose. 
(2) Whether the BY HI antibody is seroconverted in the test group (0.5mL or 0.25mL) and 

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Protocol No.: PRO-QINF-3005                                                                                
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Secondary Estimand 2 
the TIV-BV group 28 days after the second dose. 
(3) BV HI antibody titers of the test group (0.5mL or 0.25mL) and the TIV-BY group 28 
days after the second dose. 
(4) BY HI antibody titers of the test group (0.5mL or 0.25mL) and the TIV-BV group 28 
days after the second dose. 
Treatments 
As the same as the primary estimand 
Intercurrent  
Events and  
Treatment  
Strategies 
As the same as the primary estimand 
Population-level 
Summary 
(1) Difference between the SCRs of BV HI antibody of the test group (0.5mL or 0.25mL) 
and TIV-BY group 28 days after the second dose. 
(2) Difference between the SCRs of BY serum HI antibody of the test group (0.5mL or 
0.25mL) and TIV-BV 28 days after the second dose. 
(3) GMT ratios of BV HI antibodies of the test group (0.5mL or 0.25mL) and the TIV-BY 
group 28 days after the second dose. 
(4) GMT ratios of BY HI antibodies of the test group (0.5mL or 0.25mL) and the TIV-BV 
group 28 days after the second dose. 
7.3.4 Secondary Estimand 3 
Table 7 Secondary Estimand 3 
 
Secondary Estimand 3 
Population 
The target population involves the subjects (susceptible population) with the HI antibody 
titer <1:10 before immunization, aged 6 to 35 months, who have completed the full-course 
vaccination of two doses. 
Variable 
As the same as the primary estimand 
Treatments 
As the same as the primary estimand 
Intercurrent  
Events and  
Treatment  
Strategies 
As the same as the primary estimand 
Population-level 
Summary 
As the same as the primary estimand 
 
7.4 
Study plan 
This trial is a multi-center, randomized, double-blinded, and positive-controlled design. The control 
vaccine is Anflu®, two 0.25mL-dose trivalent influenza virus split vaccines (TIVs, containing a B 
Victoria lineage or B Yamagata lineage） marketed by Sinovac. This trial will be conducted on 
children aged 6 to 35 months with the informed consent of their guardians. A total of 3,300 
participants are planned to be recruited and randomly assigned to 4 groups in a ratio of 2:2:1:1, 
namely the 0.25mL-dose QIV group, 0.5ml-dose QIV group, TIV-BV group, and TIV-BY group. 
All participants receive 2 doses of the test vaccine or control vaccine according to the 0, 28-day 
immunization schedule. 

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Protocol No.: PRO-QINF-3005                                                                                
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All participants are observed for immediate reactions for 30 minutes after each dose, solicited 
systemic and local adverse events within 0-7 days, and unsolicited adverse events within 0-28 days 
after each dose. Additionally, monitoring of serious adverse events (SAEs) and adverse events of 
special interest (AESIs) is conducted from the first dose administration to 6 months after the second 
vaccination to evaluate the safety. Venous blood samples are collected from all participants before 
immunization and 28 days after the second immunization for hemagglutination inhibition (HI) 
antibody detection to assess the immunogenicity of the vaccine. 
Table 8 Study design 
Group 
Vaccines 
Sample size 
Immunization 
schedule (days) 
Blood sample 
collection (days) 
Test group 1 
Influenza Vaccine (Split Virion), 
Inactivated, Quadrivalent (0.25mL) 
1100 
0,28 
0,56 
Test group 2 
Influenza Vaccine (Split Virion), 
Inactivated, Quadrivalent (0.5mL) 
1100 
0,28 
0,56 
Control group 1 
Influenza Vaccine (Split Virion), 
Inactivated, Anflu (0.25mL, including 
BV) 
550 
0,28 
0,56 
Control group 2 
Influenza Vaccine (Split Virion), 
Inactivated, Anflu (0.25mL, including 
BY) 
550 
0,28 
0,56 
Total 
 
3300 
 
 
7.5 
Randomization and blinding 
7.5.1 Randomization 
This clinical trial is a randomized, blinded, positive-controlled design. Then, random blind code 
will be generated by a third-party randomization statistician independent of the project using the 
SAS statistical software (version 9.4) according to the preset block lengths, and the range of random 
numbers is specified in the "Randomization protocol". Vaccines are randomized and blinded 
according to random numbers. The blind code of investigational vaccines is the "List of 
Correspondence Between Investigational Vaccine Codes and Vaccine Groups", will be stored by the 
randomization statistician. 
At the same time, the randomization statistician uses SAS statistical software to generate the backup 
vaccine blind code. When the investigational vaccine is damaged, the vaccinator should report to 
the on-site technical head and the Principal Investigator to start the spare vaccine program. The 
numbers of backup vaccines are specified in the "Randomization Scheme". All investigational 
vaccines need to be re-labeled with blind labels, and the label format is detailed in "6.7 Vaccine 
Packaging". After enrollment, each subject will receive the blinded vaccine corresponding to their 
study number.  
7.5.2 Blinding 
This clinical trial adopts a double-blind design. Randomization statisticians and other blinding staff 
who did not participate in the trial performed vaccine blinding, that is, pasting the printed label on 
the designated position of each vaccine according to the blind code. The randomization statistician 

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Protocol No.: PRO-QINF-3005                                                                                
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supervises the blinding of vaccines, and guides the blinding operators to label according to the blind 
code. After completion of blinding, the blind code should be sealed by the randomization statistician. 
The entire process of blinding must be recorded. The blinding personnel must not be involved in 
other relevant work in this clinical trial or reveal the blind code to anyone who is involved in this 
clinical trial.  
Considering 0.25mL and 0.5mL investigational vaccines were used for this clinical trial, the 
following measures were taken to maintain the blind status of the study process:  
(1) Investigators engaged in vaccination and vaccine administrators must sign confidentiality 
agreements, and cannot participate in other clinical work involving research information of 
participants;  
(2) After verifying that the information of the participants is correct, the vaccine administrator 
should take out the vaccine with the corresponding number and submit it to the vaccinators in this 
group. The vaccinators must check the information of the participants again and carry out 
vaccination after confirmation; 
(3) Each participant must be vaccinated individually, meaning that there are only the vaccination 
personnel, the subject, and his/her accompanying person in the vaccination room during each 
vaccination. 
7.5.3 Emergency Unblinding 
Based on the safety of participants and other special reasons, the treatment group information of 
individual or some participants can be obtained in emergency situations in accordance with 
pre-established standard operating procedures (SOPs). For both expected and unexpected serious 
adverse events, emergency unblinding shall only be conducted when researchers must know the 
group information due to an emergency involving the subject (e.g., requiring rescue). If knowledge 
of the group information is not necessary for handling the emergency, emergency unblinding is not 
required. 
Once emergency unblinding occurs, the time, reason, and executor of the emergency unblinding 
must be recorded promptly. Meanwhile, the monitor shall be notified as soon as possible, and a 
safety event report shall be submitted to the Ethics Committee. After the trial is completed, the 
number, reasons, scope, and timing of emergency unblinding shall be described and analyzed, 
serving as a reference for the evaluation of immunogenicity and safety. 
7.5.4 SUSAR Unblinding 
In the event of a suspected unexpected serious adverse reaction (SUSAR), the sponsor needs to 
unblind the individual case report to facilitate judging the correlation between the serious adverse 
event and the trial vaccine and determining whether rapid reporting is required. 
This clinical trial adopts a blinded design. When a situation requiring SUSAR unblinding occurs, 
the non-blinded pharmacovigilance personnel shall apply to the randomization statistician via email 
for the blind code information of the corresponding subject. After unblinding, if the vaccine 
involved is the trial vaccine, it shall be submitted in accordance with the rapid reporting procedures 
and requirements; the reporting method is specified in the submission process from the sponsor to 
the regulatory authorities in "9.7.6 Reporting of Serious Adverse Events". This unblinding process 

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shall be conducted independently, and the SUSAR unblinding of individual case reports will not 
affect the implementation of the clinical trial or the analysis of the final results. 
7.5.5 Unblinding Regulations 
Unblinding of this clinical trial will be conducted after obtaining the serum test results of all 
participants at 28 days after the second dose, which will be jointly implemented by the sponsor, 
principal investigator, and statistical party. After unblinding, personnel responsible for subject 
observation, result judgment, and data verification will remain blinded until the final database is 
locked. 
7.6 
Clinical Trial Flowchart 
The flowchart of this clinical trial is shown in Figure 1. 
 
Figure 1 Flowchart of Phase III Clinical Trial 
After the volunteer's guardian signs the 
informed consent form, screening (based 
on inclusion criteria) will be conducted. 
Physical examination 
Exclusion criteria 
Eligible 
participants 
3,300 children aged 6-35 months will be randomly assigned to 4 groups in a 2:2:1:1 
ratio, all receiving 2 doses of the test vaccine or control vaccine according to the 0, 
28-day immunization schedule 
Test Group 2: 1,100, 
quadrivalent influenza 
vaccine (0.5ml -dose) 
Control Group 1: 
550, Anflu 
(containing BV) 
Control Group 2: 
550, Anflu 
(containing BY) 
Safety observation within 0-28 days after each dose of vaccination 
Collection of SAEs and AESI from month 0 to month 7 
Blood collection before and 28 days after the second dose 
Data collection and HI antibody detection 
Database locking and trial unblinding 
Statistical analysis and summary report 
Test Group 1: 1,100, 
quadrivalent influenza 
vaccine (0.25ml 
-dose) 

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7.7 
Study duration 
7.7.1 Duration of the Study 
Table 9 Study period 
Items 
Period 
Trial preparation (site selection, protocol and case report form 
design; ethical review; site registration; application to the 
Ethics Committee for Genetic Resources; database set-up; 
subject recruitment, etc.) 
3 months 
On site operation +Data collection +Antibody detection 
10 months 
Statistical analysis 
1 month 
Finish clinical study report 
1 month 
Total 
15 months 
7.7.2 Duration of Subject Participants 
The expected period is no less than 7 months for each participant. 
7.8 
Suspension and early termination 
The Criteria of the trial suspension: 
(1) Occurrence of one or more the Grade 4 vaccine-related adverse events (local and systemic), or 
fatal or life-threatening SUSARs;  
(2) Occurrence of Grade 3 or above adverse events in ＞15% participants or more, including local 
reactions, systemic reactions and vital signs.  
The Criteria of early termination of the trials:  
(1) The sponsor requests termination of the trial and provides the reasons;  
(2) EC requests termination of the trial and provides the reasons;  
(3) The requests termination of the trial and provides the reasons; and  
(4) After the clinical trial is suspended, the investigator and the sponsor shall discuss whether to 
terminate the trial or not.  
When the occurrence of adverse events meets the suspension criteria, the trial will be suspended 
first through determination of investigators and the sponsor. In case of disagreements between 
investigator and the sponsor, the investigators' judgment shall prevail. Secondly, the suspension 
shall be reported to the national drug regulatory department and EC, as well as be informed to the 
participants. On the basis of analyzing the relevance of the adverse events as well as the severity 
and safety risks, an investigation report will be formed. Relevant parties to jointly decide whether to 
continue the clinical trial. 
7.9 
Protocol deviation 
Protocol deviation refers to any non-compliance with the clinical trial protocol design or procedures. 
Protocol deviation includes the behaviors that have no effect on the rights and interests, safety and 
benefits of the participants, or the completeness, accuracy and reliability of the trial data, as well as 
the evaluation on the safety or key indicators of the protocol; and major protocol deviation (protocol 

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violation) includes affecting the rights, interests, safety and benefits of participants, or the integrity, 
accuracy and reliability of test data, as well as the evaluation of endpoints.   
Participants with major protocol deviations should be given special attention, and safety 
information should be collected to ensure their safety. For any protocol deviation occurring during 
the study, investigators shall record it in detail, report it to the principal investigator and the sponsor, 
and submit it to the EC as required. The principal investigator and the sponsor shall determine 
whether participants with protocol deviations will continue to complete the subsequent study 
procedures. 
The list of major protocol deviations includes (but is not limited to): 
(1) Failure to obtain informed consent from the participants' guardians; 
(2) Enrollment of participants who do not meet the inclusion criteria or meet the exclusion criteria; 
(3) Incorrect vaccination of participants with the trial vaccine; 
(4) Report serious adverse events (SAEs) without the specified time; 
(5) Vaccination with any influenza vaccine other than the trial vaccine during the study period; 
(6) Vaccination of the trial vaccine outside the window period; 
(7) Blood collection outside the window period; 
(8) The interval between vaccinations does not meet the requirements (including emergency 
vaccination in response to urgent events).  
8. Participants 
8.1 
Inclusion criteria 
(1) Children in stable health aged 6-35 months; 
(2) Children’s guardians are able to provide legal identity documents and immunization certificates;  
(3) Obtain the written informed consent of the participant's guardian; 
8.2 
Exclusion criteria for the first dose of vaccination 
(1) History of the seasonal influenza vaccine for the 2023-2024 influenza season, or have a 
vaccination schedule during the trial;  
(2) History of seasonal influenza in the past 6 months;  
(3) Axillary temperature >37.0°C before vaccination;  
(4) History of allergy to the vaccine or vaccine ingredients, and have serious adverse reactions to 
the vaccine, such as urticaria, dyspnea, and angioneurotic edema;  
(5) Congenital malformations or developmental defects, genetic defects, severe malnutrition, or 
asthma;  
(6) Serious chronic diseases (Down's syndrome, diabetes, or sickle cell anemia);  
(7) Severe nervous system disorder (epilepsy, seizure or convulsion) or psychotic disorder;  
(8) Autoimmune 
diseases 
(e.g., 
systemic 
lupus 
erythematosus) 
or 
immunodeficiency/immunosuppression (e.g., AIDS, post organ transplant);  
(9) History of thyroidectomy, asplenia, functional asplenia, and asplenia or splenectomy under any 
circumstance;  
(10) Coagulation abnormalities (such as coagulation factor deficiency, coagulation disease and 
platelet disorder), obvious bruise or coagulation defects from a doctor's diagnosis;  
(11) Has received continuous treatment with corticosteroids or other immunosuppressants 
(excluding corticosteroid spray therapy for allergic rhinitis and surface corticosteroid therapy for 

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acute uncomplicated dermatitis) and cytotoxic therapy for ≥14 days in the past 6 months;  
(12) Acute diseases in recent 3 days;  
(13) Has received blood products in past 3 months;  
(14) Has received other investigational drugs within 30 days;  
(15) Has received live attenuated vaccines within 14 days or subunit or inactivated vaccine within 7 
days;  
(16) Has participated in other clinical trials before enrollment and is within the follow-up period, or 
plan to participate in other clinical trials during the clinical trials;  
(17) Any other factors that are inappropriate for participation in the clinical trial by investigator's 
judgment. 
8.3 
Exclusion criteria for the second dose of vaccination 
If one of the following (1) to (4) conditions occur, the participant is not allowed to continue 
vaccination at the discretion of the investigator. If one of the following (5) to (6) conditions occur, 
the investigator shall determine whether the participant continues vaccination. If one of the 
following (7) to (10) conditions occur, the participant may receive postponed vaccination within the 
time window specified in the protocol.  
(1) Influenza vaccine other than the investigational vaccine is used during the study;  
(2) Any SAEs related to vaccination of participants occur;  
(3) Severe allergic reaction or hypersensitivity reaction occurs after vaccination (including 
urticaria/rash within 30 min after vaccination);  
(4) Any confirmed or suspected autoimmune or immunodeficiency disease occurs, including human 
immunodeficiency virus (HIV) infection; 
(5) Acute onset of chronic disease or emerging chronic disease occurring after vaccination;  
(6) Other reactions occur as judged by the investigator, including severe pain, severe swelling, 
severe limitation of motion, persistent hyperpyrexia, severe headache or other systemic or local 
reactions;  
(7) An acute disease occurs at the time of vaccination (acute disease is a moderate or severe disease 
with or without pyrexia);  
(8) Axillary temperature＞37.0°C; 
(9) The subunit vaccine or inactivated vaccine is inoculated within 7 days, or the live attenuated 
vaccine is inoculated within 14 days;  
(10) Any other factors that are inappropriate for vaccination by investigator's judgment. 
 
8.4 
Criteria for withdrawal and termination 
(1) The participant's guardian request to withdraw from the clinical trial;  
(2) Occurrence of intolerable adverse events, whether it is related to the experimental drug or not;  
(3) The health condition of the participant does not permit participation in this study;  
(4) Upon any abnormal clinical manifestations, the participants will be determined by the 
investigator whether they are related to the vaccine and whether the participants will discontinue 
the clinical trial early;  
(5) Any other causes judged by the investigators.  
If the participant who discontinues the clinical trial early has received the test vaccine, the clinical 
trial data of the participant will be used for safety analysis. The participants cannot be replaced 

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Protocol No.: PRO-QINF-3005                                                                                
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during the study. After withdrawal or discontinuation of a trial in a participant who has received the 
clinical test vaccine, the investigator shall provide the necessary guidance to the participant in any 
clinical conditions that may arise in connection with the trial and continue the follow-up until the 
definitive diagnosis established/stable condition/recovery. 
9. Study procedure 
9.1 
Schedule of activities 
Table 10 Schedule of activities 
Visit Number 
0 
1 
2 
3 
4 
5 
6 
Visit date 
D-14-0 
D0 
D7d 
D28 d 
D35 d 
D56 d 
D208 d 
Preliminary 
notice, 
participant 
enrollment 
X 
 
 
 
 
 
 
Informed consent 
 
X 
 
 
 
 
 
Demography 
 
X 
 
 
 
 
 
Medical history collection 
 
X 
 
 
 
 
 
Physical examination 
 
X 
 
 
 
 
 
Screening by the inclusion/exclusion 
criteriaa 
 
X 
 
X 
 
 
 
Blood collection 
 
X 
 
 
 
X 
 
Vaccinationb 
 
X 
 
X 
 
 
 
The participants or their 
guardians/caregiver record safety 
observations on the diary card/contact 
cardc 
 
X 
X 
X 
X 
X 
 
Monitoring 
of 
adverse 
reactions/events (including grade 3 
and above adverse events, SAE, 
AESI) c 
 
X 
X 
X 
X 
X 
X 
Record 
of 
the 
concomitant 
medication/the vaccine usage c 
 
X 
X 
X 
X 
X 
X 
a) Screening by inclusion/exclusion criteria should be performed before each dose of 
vaccination.  
b) The participants will be observed for 30 minutes to confirm occurrence of adverse event, 
especially that of acute anaphylaxis; and they will be followed up as required.  
c) Safety observation includes evaluation of the adverse reactions/events and body temperature 
measurements, the latter of which should be taken daily from day 0 to 7 after the vaccination 
or when the fever is suspected. The participants record the safety observations on their diary 
cards within 28 days of each dose of vaccination, and the investigators shall interview the 
participant regularly to verify and document the adverse events and concomitant 
medication/the vaccine usage.  
d) Please refer to the “Visit plan” for the time window. 
 
Visit plan:  

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Visit 0 -day -14~0 - Preliminary notice, participant enrollment;  
Visit 1 -day 0 - Enrollment of the eligible participants, blood collection and vaccination of the first 
dose;  
Visit 2 -day 7 (+3 days) after the first dose - verify the safety observation, medication and other 
vaccination records;  
Visit 3 -day 28 (+15 days) after the first dose - verify the safety observation, medication, other 
vaccination records and vaccination of the second dose; 
Visit 4 -day 7 (+3 days) after the second dose - verify the safety observation, medication and other 
vaccination records;  
Visit 5 -day 28 (+15 days) after the second dose - verify the safety observation, medication, other 
vaccination records and blood collection; 
Visit 6 -day 180 (+30 days) after the second dose - verification of SAE and AESI observations, 
records of concomitant medication use, and other special circumstances through telephone 
follow-up. 
During the clinical trial, if an SAE or AESI occurs, the participant's guardian shall be contacted to 
assist in providing the corresponding medical records, and efforts shall be made to complete the 
information collection. If it is indeed impossible to collect the information, "unknown" shall be 
noted in the relevant information section of the original records. 
9.2 
Enrollment and informed consent 
Distribute the recruitment notice to the guardians of potential participants. Explain the informed 
consent to the participant in detail. On the basis of voluntary participation, the informed consent 
will be signed by the participant’s guardian and the investigation physician in duplicate; and the 
participant holds the duplicate. Participants will be recruited in accordance with "8.4 Study Plan". 
9.3 
Screening and randomization 
Volunteers recruited will undergo physical examination with no abnormalities and be screened 
against inclusion/exclusion criteria. The screening number will be formatted as "S + on-site code + 
screening sequence number", for example, "SZ0001". Eligible participants after screening will be 
enrolled and assigned a unique study number in the order of enrollment. Once a study number is 
assigned, it shall not be reassigned to any other subject. For researchers' numbers of participants, 
see "7.5.1 Randomization". 
9.4 
Vaccination 
The information of participant and trial vaccine should be checked before the vaccination, and only 
those who meet the inclusion and exclusion criteria of this clinical trial protocol can be vaccinated. 
Please refer to “5.5 Route and Schedule of Vaccine Administration” for Immunization Schedule. 
9.5 
Safety follow-up observation 
Observe the participants on-site for adverse events within 30 minutes after each dose of vaccination; 
and give the participants the diary cards after each dose to record the solicited adverse events 
(systemic and local) from day 0 to 7 after the vaccination and unsolicited adverse events from day 0 
to 28 after the vaccination. Investigators will explain the judgment of adverse events, measurement 
methods, recording methods, precautions, reporting methods, etc., and distribute diary cards, rulers, 

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Protocol No.: PRO-QINF-3005                                                                                
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and thermometers. They will also train the participant's guardian on using the thermometer, 
observing adverse events, filling in the diary card, and make an appointment for the return time. 
Request the subject's guardian to fill out the diary card in detail from day 0 to 28 after the 
vaccination to record any clinical symptoms, medications and the use of other vaccines. 
Conduct systematic observation 0-7 days after each dose of vaccination. The participant's guardian 
observes the subject's symptoms and signs every day and fill them in the diary cards for the 
investigators to collect safety observation data from day 0 to 7. From day 8 to 28, record the adverse 
events by using the method of voluntary reporting from subject's guardian and regular follow-up by 
investigators; and at day 28, take back the diary cards. Monitoring of SAEs) and AESIs will 
continue until 6 months after the second of vaccination. SAEs and AESIs from day 29 after the 
second of vaccination to 6 months after the second will be collected through a combination of 
telephone follow-up once every 2 months and active reporting by the subject. 
The participants should be informed of recording any adverse events at any time. In case of acute 
allergic reaction, Grade 3 or above adverse event or SAE, they should report to the investigators at 
any time and the investigators should conduct investigation, verification, and follow-up after 
learning until the event is resolved so as to finally complete the detailed investigation and follow-up 
records, which should include following:  
- Description of adverse events  
- Start time and end time of adverse events  
- Severity classification of adverse events  
- Correlation with the vaccination  
- Laboratory results  
- Treatment  
If an acute allergic reaction occurs after vaccination, emergency treatment should be provided in 
time to relieve the pain of the participants as soon as possible. In case of grade 3 or above adverse 
event or SAE after vaccination, medical advice should be given in a timely manner; if necessary, the 
relevant on-site responsible personnel may be contacted to activate the green channel for medical 
treatment. The medication and medical treatments during each follow-up visit should be recorded in 
detail. If an AESI occurs (see 9.7.1), the investigators should make a judgment based on clinical 
symptoms and signs. When necessary, clinical samples (such as blood, urine, etc.) should be 
collected for laboratory tests, relevant questionnaires should be filled out, and follow-up should be 
conducted until the AESI is resolved. 
9.6 
Blood sample collection 
All participants will have approximately 2-3 ml of venous blood collected before immunization and 
28 days after the second of vaccination, respectively. The serum will be separated for antibody 
detection. The sample numbering rule is "Study Number + Collection Sequence Number". 
All samples collected on-site shall be promptly sent to the laboratory, and handover with laboratory 
personnel shall be completed. Laboratory personnel shall promptly separate the serum from blood 
samples for serum antibody detection and aliquot them into 2 tubes (Tube A of the blood sample set 
should contain no less than 0.5 ml for serum antibody detection; Tube B is the backup serum). After 
serum separation, it should be promptly frozen and stored at -20°C or below. Records should be 
kept for sample handover, separation, and storage. For all submitted samples, a specimen 

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Protocol No.: PRO-QINF-3005                                                                                
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submission record should be filled out, and temperature control records during the submission 
process should be retained. 
9.7 
Safety Evaluation 
9.7.1 Index for the safety observation 
Solicited local adverse events (at the vaccination site): tenderness/pain, induration, swelling, 
erythema, rash, pruritus.  
Solicited systemic adverse events (including vital signs) (non-vaccination site): fever (axillary 
temperature), acute allergic reaction, skin and mucosal abnormalities, diarrhea, anorexia, vomiting, 
nausea, cough, fatigue, irritability, lethargy. 
See "9.7.7 Safety Evaluation Criteria" for details. 
Adverse events of special interest (AESI): include Guillain-Barré Syndrome (GBS), convulsion, 
encephalitis, myelitis, neuritis, Bell's palsy, vasculitis, thrombocytopenia. 
9.7.2 Definition of adverse event/reaction 
Vaccine safety will be evaluated based on the severity of the local adverse events, systemic adverse 
events and vital signs as well as their relevance to the vaccination.  
All adverse medical events occurring during the trial (i.e. from the signing of informed consent) 
will be collected and recorded. 
(1) Adverse event (AE): All adverse medical events that occur in a clinical trial participant after 
receiving an experimental vaccine may be manifested as symptoms and signs of illness or abnormal 
laboratory tests, but unnecessarily have any causal relationship with an experimental vaccine. 
(2) Adverse reaction: Any harmful or undesirable reaction to humans that may be associated with an 
experimental vaccine during a clinical trial. A causal relationship between an experimental vaccine 
and an adverse event is at least a reasonable possibility in which the relevance cannot be ruled out.  
(3) Serious adverse event (SAE): Refers to any of the following events occurring in clinical trial 
participants after receiving the trial vaccine: 
• Result in death.  
• Is life-threatening: An event where the participant is at risk of death at the time of the 
adverse event's onset; it does not refer to an event which hypothetically might have 
caused death if it were more severe.  
• Requires inpatient hospitalization or prolonged of existing hospitalization: (Routine 
hospital admission such as for antenatal care, labor & delivery is not an SAE) 
• Results in a persistent or significant disability or incapacity  
• Results in congenital anomalies or birth defects.  
• Any other significant medical events (that may not cause death, be life threatening, or 
require hospitalization) that may, based upon appropriate medical judgment, jeopardize 
the participant and/or require medical or surgical intervention to prevent one of the 
outcomes listed above. Examples of such medical events include allergic reaction 
requiring intensive treatment in an emergency room or clinic, blood dyscrasias, or 

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Protocol No.: PRO-QINF-3005                                                                                
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convulsions that do not result in inpatient hospitalization. 
Events not considered as serious adverse events: 
• Routine emergency room visits (including 24-hour observation stays); 
• Hospitalization for routine outpatient examinations; 
• Hospitalization for social reasons: Such as hospitalization of the subject due to lack of care; 
• Hospitalization for surgery scheduled before signing the informed consent form, but if the 
condition worsens requiring early surgery, it is considered an SAE; 
• Routine physical examination hospitalization; 
Death itself is an outcome and not regarded as an SAE. The primary cause of death (the main 
adverse event leading to death) shall be recorded and reported as an SAE. "Death" shall be reported 
as a consequence of the corresponding adverse event. If there is no definite cause for death to report, 
death itself may be reported as an SAE. 
 (4) Suspected and unexpected serious adverse reaction (SUSAR): is a suspected and unexpected 
serious adverse reaction, for which, the nature and severity of the clinical manifestations exceed the 
existing information provided in the brochure of the experimental drug investigators, manual of the 
on-market drugs or summary of product characteristics, etc. 
 (5) Solicited/unsolicited adverse events: in this study, the solicitation period is from day 0 to 7 
after each dose of vaccination, and the unsolicited period is from day 8 to 28. The solicited 
symptoms occurring during the solicitated period are referred to as the solicited adverse events and 
other symptoms during the solicitated period; and all the symptoms during the unsolicited period 
are referred to as the unsolicited adverse events. 
9.7.3 Outcomes of adverse events 
Outcomes of adverse events include: (1) recovered, (2) not recovered, (3) recovered with sequelae, 
(4) recovering, (5) death and (6) lost/unknown. 
9.7.4 Correlation of adverse events and vaccines 
The investigators should do their best to explain AE and to evaluate its possible causality, that is, 
the causality between the investigated vaccine and the alternative causes (such as history of 
underlying disease and the combined treatment), which applies to all AE, both serious and 
non-serious.  
Causality assessments will be determined by the extent to which the events can be reasonably 
explained in one or more of the following:  
A reasonable temporal relationship between the administration of the trial vaccine and the 
occurrence of adverse events 
Reactions of similar nature have previously been observed in this type of vaccine;  
Same events have been reported in the literature with regard to the similar types of vaccine;  
The occurrence of the event coincided with the vaccination of the administration of the 
investigational vaccine; and occur again after the re-administration of the vaccine.  
The occurrence of the event can be explained by the effects of concomitant medications (vaccines) 
or the impact of other treatments  

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AE Causality should be assessed, by the investigator, to ensure whether there is a reasonable 
possibility that the AE is caused by the administration of the vaccine, based on the following: 
General principles for the correlation judgment:  
✓ Certainly related: there is evidence of vaccination with the experimental vaccines; the 
occurrence of adverse events and the time sequence of the test vaccine administration are 
reasonable; adverse events are more likely to be explained by the test vaccines than by other 
causes; positive results after repeated administration of the test vaccine; adverse events are 
consistent with the prior knowledge of this type or these types of the vaccine.  
✓ Probably related: there is evidence of vaccination with the experimental vaccines; the 
occurrence of adverse events and the time sequence of the test vaccine administration are 
reasonable; adverse events are more likely to be explained by the test vaccines than by other 
causes.  
✓ Possibly related: there is evidence of vaccination with the experimental vaccines; the 
occurrence of adverse events and the time sequence of the test vaccine administration are 
reasonable; the occurrence of the adverse events cannot be ruled out as a result of the test 
vaccine and possibly may be caused by other reasons.  
✓ Unlikely related: there is evidence of vaccination with the experimental vaccines; adverse 
events are more likely to be caused by other factors; repeated vaccination tests are negative 
or uncertain.  
✓ Not related: the participants do not use the test vaccine; or the occurrence of adverse 
events and the time sequence of the test vaccine administration are unreasonable; or there 
may be other significant factors for the adverse events.  
9.7.5 Management of adverse reactions/events  
After vaccination, grade 1 or grade 2 adverse reactions, such as redness, swelling, pain or (and) 
fever and general malaise etc. can disappear automatically, without any special treatment.  
The investigators should conduct the investigation and follow-up on the adverse reactions/events 
occurred in the participants from the beginning of the immunization to day 28 after the second of 
the immunization, including medical history, physical examination and necessary laboratory 
examination, treatment and follow-up until the events are resolved.  
9.7.6 Report serious adverse events 
(1) Reporting Procedures for Investigators 
The study institutions shall establish an emergency response plan for SAE handling. Upon learning 
of an SAE, regardless of whether it is related to the trial vaccine, the investigator must immediately 
(within 24 hours as required) fill out the Serious Adverse Event Report Form, send the initial report 
to the sponsor (via the dedicated pharmacovigilance email for clinical trials: safety@sinovac.com), 
and copy the report administrator. In case of emergency, the 24-hour emergency contact can also be 
reached (Name: Zhang Caiquan; Contact information: 15210086226). Subsequent supplementary 
information/reports shall be submitted as soon as possible until the event is resolved. 
When filling out the Serious Adverse Event Report Form, the investigator shall report the entire 
situation in writing, including but not limited to the name and relevant description of the adverse 
event, the occurrence time and type of the SAE, duration, severity, causal relationship with 

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vaccination, outcome, measures taken (symptomatic treatment), and other relevant clinical and 
laboratory data. 
In case of a death event, the investigator shall report to the sponsor and the EC, and provide the 
autopsy report and final medical report. 
Meanwhile, the clinical trial responsible institution/investigator shall promptly forward the 
sponsor's latest safety information reports on the clinical trial to the EC. 
The EC shall receive SAE reports and other safety information reports, keep abreast of the 
occurrence and handling of SAEs throughout the clinical trial, and conduct follow-up reviews on 
the handling and reporting of SAEs during the trial. 
(2) Reporting Procedures for the Sponsor 
The day on which the sponsor first becomes aware of a valid report is designated as Day 0. After 
receiving the SAE reported by the investigator, the sponsor's pharmacovigilance personnel shall 
immediately review the completeness and accuracy of the original data. If necessary, they shall send 
inquiries to the investigator. At the same time, the sponsor shall analyze and evaluate the report, 
including the severity, relevance to the trial vaccine, and whether it is an unexpected event. 
During the drug clinical trial, for adverse reactions determined to be SUSARs, the sponsor's 
pharmacovigilance personnel shall submit SUSAR reports to the national drug regulatory 
authorities and health authorities in accordance with the requirements of the Drug Registration 
Administration Measures [1], Good Clinical Practice [2], and Standards and Procedures for Rapid 
Reporting of Safety Data During Drug Clinical Trials [28]. If the investigator and the sponsor cannot 
reach an agreement on the causal relationship between the adverse event and the drug, and either 
party judges that the relationship with the investigational vaccine cannot be ruled out, the sponsor 
shall also submit a rapid report. 
The sponsor shall submit SUSAR reports to all investigators, study institutions, and ethics 
committees participating in the clinical trial. Investigators shall promptly read the reports provided 
by the sponsor and submit the signed reports to the ethics committee. 
For SUSAR that are non-fatal or non-life-threatening, the sponsor shall report them as soon as 
possible after first becoming aware, but no later than 15 calendar days; for unexpected serious 
adverse reactions that are fatal or life-threatening, the sponsor shall report them as soon as possible 
after first becoming aware, but no later than 7 calendar days, and submit and complete follow-up 
information within the subsequent 8 calendar days. 
9.7.7 Grading of Adverse events 
The solicited local adverse events and unsolicited systemic adverse events: The classification 
criteria for solicited adverse events are mainly referred to the “Guidelines for criteria classification 
for adverse events in clinical trials of prophylactic vaccines” [29] (2019) issued by NMPA, as shown 
in the table below. The solicited adverse events and unsolicited adverse events with the same 
symptoms are classified according to the following: 
Table 11 Grading of local solicited adverse events 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Tenderness (6-23 
Resistance or 
Crying upon contact 
Persistent crying and 
Requiring emergency 

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Protocol No.: PRO-QINF-3005                                                                                
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months old) 
withdrawal 
upon contact or 
touch 
or touch, but 
consolable 
unconsolable 
treatment or 
hospitalization 
Pain (24-35 
months old) 
Not affect or 
slightly affect 
limb activity 
Affect limb activity 
Affect daily life 
Loss of basic self-care 
ability, or hospitalization 
Induration* 
#, 
Swelling# 
＜2.5cm in 
diameter 
≥2.5cm in diameter 
and <50% of the 
vaccinated limb 
(anatomically the 
limb where the 
vaccinated site is 
located, e.g. upper 
arm or thigh) in area 
≥50% of the vaccinated 
limb 
or 
ulcerated 
or 
secondary 
infection 
or 
phlebitis 
or 
wound 
drainage in area 
Abscess, 
exfoliative 
dermatitis, 
dermal 
or 
deep tissue necrosis 
Redness#, rash* # 
＜
2.5cm 
in 
diameter 
≥2.5cm in diameter 
and <50% of the 
vaccinated 
limb 
(anatomically 
the 
limb 
where 
the 
vaccinated 
site 
is 
located, e.g. upper 
arm or thigh) in area 
≥50% of the vaccinated 
limb 
or 
ulcerated 
or 
secondary 
infection 
or 
phlebitis 
or 
wound 
drainage in area 
Abscess, 
exfoliative 
dermatitis, 
dermal 
or 
deep tissue necrosis 
Pruritus 
Pruritus at the 
vaccination site, 
but will be 
relieved without 
any treatment or 
within 48 hours 
after treatment 
Pruritus at the 
vaccination site, and 
will not be relieved 
within 48 hours after 
treatment 
Affect daily life 
NA 
* In addition to directly measuring the diameter of induration and rash for grading, the progress of the measurements should also be 
recorded.  
# The largest diameter or area of the induration, swelling, rash and redness should be measured; and the evaluation and grading 
should be based on the functional grade and actual measurement results, selecting the higher grading index. 
Table 12 Grading of systemic solicited adverse events 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Acute allergic 
reaction* 
Local urticaria  
(blister), treatment  
not required 
Local urticaria (blister), 
treatment required; or 
mild angioedema, 
treatment not required 
Generalized urticaria 
or angioedema, 
treatment required; or 
mild bronchospasm 
Allergic shock, or 
Life-threatening 
bronchospasm, or 
laryngeal edema 
Skin and mucosal 
abnormalities 
Erythema/pruritus/c
olor change 
Diffuse 
Rashes/maculopapules/d
ryne ss/desquamation 
Blistering/exudation/ 
desquamation/ulcer 
Exfoliative 
dermatitis 
involved mucosa, 
or erythema 
multiforme or 
suspected 
Stevens-Johnsons 
syndrome 
Diarrhea 
Slight or transient, 
3 ～4 
times/day; 
abnormal 
fecal 
character, or slight 
diarrhea 
lasting 
shorter than 1 week 
Mild or transient, 5～7 
times/day; 
abnormal 
fecal character, or mild 
diarrhea lasting longer 
than 1 week 
>7 
times/day; 
abnormal 
fecal 
character, or bloody 
diarrhea, 
orthostatic 
hypotension 
or 
electrolyte imbalance, 
intravenous 
infusion >2L required 
Hypotension 
and 
shock, 
hospitalization 
required 
Anorexia 
Appetite decreased, 
without food intake 
reduced 
Appetite decreased, with 
food intake reduced, but 
without 
significant 
Appetite 
decreased, 
with significant weight 
loss 
Intervention 
required (eg. tube 
feeding and for 

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Grade 1 
Grade 2 
Grade 3 
Grade 4 
weight loss 
parenteral 
nutrition) 
Vomiting 
1~2 times/24 hours, 
without affecting the 
movement 
3~5 times/24 hours, or 
affect the movement  
＞6 times/24 hours, or 
intravenous 
infusion 
required  
Hypotensive 
shock, 
hospitalization 
require, or other 
means of nutrition 
required 
Nausea 
Transient 
( ＜24 
hours), 
or 
Intermittent 
and 
with 
food 
intake 
generally normal  
Persistent nausea leads 
to food intake reduced 
(24～48 hours) 
Persistent nausea leads 
to food intake very 
little (> 48 hours), or 
intravenous 
infusion 
required 
Life 
threatening 
(e.g. 
hypotensive 
shock) 
Cough 
Transient, 
no 
treatment required 
Persistent 
cough, 
treatment effective 
Paroxysmal 
cough, 
uncontrollable 
by 
treatment 
Emergency 
treatment 
or 
hospitalization 
Fatigue 
Normal movement  
Normal 
movement 
reduced 
Severely affecting the 
movement and unable 
to work 
Emergency 
treatment 
or 
hospitalization 
required 
Irritability 
Mild irritability 
Irritable 
Unsoothable 
NA 
Lethargy 
Mild lethargy 
Drowsiness 
Hyporesponsiveness 
NA 
Vital signs-  
Fever, 
axillary 
temperature (℃) 
37.5～＜38.0 
38.0～＜39.5 
≥39.5 
≥39.5, 
for 
successively 
5 
days 
*refers to hypersensitivity of Type I. 
For the adverse events not included in the above grading tables, the severity of adverse events is to 
be graded according to the following grading criteria:  
Mild (Grade 1): short duration (<48h) or slight discomfort, without affecting the movement and no 
treatment is required;  
Moderate (Grade 2): Mild or moderate movement is limited, and medical attention might be 
required, but with no or only mild treatment;  
Severe (Grade 3): Movement is limited significantly, requiring medical attention and treatment, and 
might require hospitalization; and  
Critical (Grade 4): The critical illness can be life threatening, severely limiting the movement and 
requiring Intensive Care.  
Grade 5: Death 
9.8 
Concomitant medications and vaccines 
9.8.1 Concomitant medications 
(1) Upon the occurrence of adverse events during the trials, it is allowed to conduct some necessary 
treatments and medical treatments.  
(2) When severe allergic reactions or life-threatening reactions occur, first aid measures should be 
taken immediately.  
(3) The investigators should record the information about any drug combinations, including names, 
dosage forms, dosages and time of use, etc. 

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Protocol No.: PRO-QINF-3005                                                                                
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9.8.2 Concomitant vaccines 
(1) Other vaccines shall be administered at least 7 days after receiving the investigational vaccine.  
(2) During the trial when emergency vaccines are needed, the participants should get vaccinated, 
such as rabies and tetanus vaccine.  
(3) For concomitant vaccines, detailed information should be recorded, including their names, 
usages and time of the vaccination. 
9.8.3 Record of Concomitant Medications and Vaccines 
To understand and rule out the impact of concomitant medications and vaccines administered 
during the trial on the safety and immunogenicity of the trial vaccine, as well as to collect all 
possible adverse events that may be related to vaccination, investigators shall guide participants' 
guardians to record details of medical visits, concomitant medications, and vaccines in the diary 
card as much as possible. In the event of an SAE or AESI, the participant's guardian shall be 
contacted to assist in providing the corresponding medical records, and efforts shall be made to 
complete the information collection. If it is indeed impossible to collect the information, "unknown" 
shall be noted in the relevant section of the original records. 
9.9 
Immunogenicity evaluation 
The immunogenicity endpoints are SCR, SPR, GMT and GMI of influenza HI antibody of each 
strain. 
9.9.1 Definitions 
SCR: The percentages of participants with either a pre-vaccination titer <1:10 and a 
post-vaccination titer ≥1:40, or a pre-vaccination titer ≥ 10 and a ≥ 4-fold increase in 
post-vaccination titer  
Seroprotection: HI antibody titer is ≥1:40. 
9.9.2 Laboratory test method 
Micro-hemagglutination inhibition test will be used to test the antibody. 
9.10 Data management 
9.10.1 Source Data  
The source Data shall include the informed consent, diary cards and original records, etc., which 
record the following basic data:  
• 
Name of the trial and participant number; 
• 
Demographic data;  
• 
Inclusion/exclusion criteria;  
• 
Vaccination record;  
• 
The date of the follow-up and the date the participants terminate the trials; 
• 
Adverse events/reactions and their management and outcome;  
• 
Concomitant medical treatment and other vaccinations;  

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All data should be recorded in source documents, which should be properly stored in a specialized 
space by the investigator. The original data should be archived at the study site, which is the basis of 
the participants' participation in the clinical trials and the true integrity of the data.  
The investigators should keep the original records carefully, accurately and timely; and all the 
collected original data should be recorded on the same day. It is required to fill in the record with a 
black pen. Any errors should not be altered, but be underlined and fill in the correct next to it, and 
signed with name and the date. 
9.10.2 Design of eCRF 
The eCRF is designed in accordance with the trial procedures and flowcharts specified in the 
protocol. After the first draft is formed, it needs to be jointly reviewed by members of the project 
team including the sponsor, project manager, medical personnel, data personnel, and statistical 
personnel. It shall conform to the protocol and relevant laws and regulations, and the version 
control process shall be completely recorded. 
9.10.3 eCRF Completing Guidelines 
The eCRF completing guidelines are specific instructions for filling in each page of the eCRF and 
each data point. It is ensured that the clinical trial center obtains the eCRF and its completing 
guidelines before enrolling participants, and trains the relevant staff of the clinical trial center on the 
eCRF filling and data submission process. This process shall be archived and recorded. 
9.10.4 eCRF Annotations 
The annotated eCRF is the marking of the blank eCRF, which records the position of each data item 
in the eCRF as well as its variable name and code in the database. All data items in the eCRF need 
to be annotated. 
9.10.5 Database Design 
The database shall be established in accordance with the dataset name, variable name, variable type, 
and variable length in the annotated eCRF, and shall comply with the structure and settings of the 
standard database as much as possible. After the database is established, database testing shall be 
conducted, and it can be used only after passing the test. 
9.10.6 Permission Allocation 
The system administrator shall create accounts for different roles and grant different permissions 
respectively. 
9.10.7 eCRF Filling 
Investigators shall collect participants’ data in accordance with the requirements of the study 
protocol, and accurately, timely, completely, and standardly fill the information into the eCRF based 
on the original data with reference to the filling guidelines. Any modification to eCRF data must 
comply with standard operating procedures, and modification traces shall be retained. 
9.10.8 Issuance and Resolution of Queries 
The data management (DM) department shall formulate a detailed data verification plan. After the 
verification plan is reviewed and approved by the sponsor, medical personnel, statisticians, project 

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Protocol No.: PRO-QINF-3005                                                                                
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managers, etc., it shall be signed and confirmed by data administrators, data managers, and the 
sponsor. After data is entered into the eCRF in the EDC system, the system will verify the data in 
accordance with the Edit Checks established in the data verification plan. Data with doubts will 
automatically trigger system queries; data that cannot be set to trigger system queries will be sent 
manual queries through the EDC. Investigators shall confirm and respond to manual and system 
queries, and modify incorrect data if necessary until the queries are resolved. If the response fails to 
resolve the query, data administrators and clinical monitors may issue a re-query for the data point. 
All traces shall be stored in the EDC database. 
9.10.9 Data Modification and Review 
Investigators may modify data after verifying it. For modified data, the modification reason shall be 
filled in the system as prompted. Researchers have the authority to review all final data. 
9.10.10 Medical Coding 
Participants' medical history, as well as AEs and SAEs during the clinical trial, shall be coded using 
standard dictionaries. The commonly used standard dictionary is the Medical Dictionary for 
Regulatory Activities (MedDRA). The dataset after coding shall clearly record the dictionary and 
version used for coding. 
9.10.11 Data Review Meeting 
Before database locking, the draft data review report and all data lists shall be prepared. The 
sponsor, investigators, data management personnel, and statistical analysts shall jointly conduct the 
final review of the database, including the division of statistical analysis populations in accordance 
with the clinical trial protocol, verification of records of SAE reporting and handling, etc. After the 
data review meeting, the data management report and population division plan shall be finalized. 
9.10.12 Database Lock and Unlock 
Database lock is an important milestone in the clinical research process. The lock process and time 
shall be clearly documented. Database lock means revoking the permission to edit the database, and 
no unauthorized account shall be able to operate the database. 
If modifications are required after the database is locked, an application shall be submitted. The 
modification can only be implemented after discussion and signature confirmation by the sponsor, 
investigators, clinical monitors, and data management personnel, and the reasons for unlocking 
shall be recorded in detail. 
9.11 Statistical Analysis 
This section was did not translated from Chinese to English. Please see statistical analysis plan 
(SAP). 
10. Monitoring of the clinical trials 
10.1 Responsibilities of the sponsor 
The sponsor shall implement and maintains the quality assurance and quality control, responsible 
for quality management to ensure that the trials are carried out according to local regulations, GCP 
and the protocol. 

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Protocol No.: PRO-QINF-3005                                                                                
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10.2 Responsibilities of the investigators 
The Principal Investigator should provide management and clear labor division for all personnels in 
the clinical trials. The investigator should keep the personal data of the participants confidential. 
Documents provided to the sponsor should be identified only by the participant code and participant 
number. The identification list of the participants will be maintained by the investigators in their file. 
In accordance with the GCP principle, the original data of each participant is allowed to be 
monitored, checked and reviewed. 
10.3 Personnel training 
Before the trial, the personnel should be trained. The training should include: GCP, clinical trial 
protocol and SOP, etc. If additional CRAs or investigators are added during the trial, they should be 
trained individually. Retraining may be conducted as deemed necessary by the sponsor or the 
Principal Investigator. Each training should be recorded. 
10.4 Participant compliance assurance 
According to the clinical trial protocol, a succinct, clear and coherent volunteer enrollment 
notification and informed consent shall be developed.  
Train the informed consent explainers to communicate with the volunteers using plain language so 
as to ensure the volunteers to be fully informed.  
Screen the participants strictly according to the inclusion/exclusion criteria.  
Follow-up personnel should be responsible and professional, improving their communication skills 
and affinity through training. During the safety follow-up, take measures to ensure effective contact 
between the participants and the investigators, timely disposal of any adverse reactions found and 
provide the relevant health consultations to the participants. 
For participants who fail to comply with the visit plan and have not received subsequent vaccine 
doses for non-safety reasons, investigators shall contact the participants' guardians to complete the 
subsequent vaccine administration and visits in accordance with the vaccination procedures and 
visit plan specified in the trial protocol. 
The trial site is responsible for ensuring that study visits for each participant are within time window. 
If a participant misses a scheduled visit, every effort shall be made to contact the participant 's 
guardian and complete the visit within the specified visit window. If the participant fails to complete 
the visit within the window, the participant will continue to complete the subsequent scheduled 
visits. 
10.5 Investigational vaccine management 
10.5.1 Definition and handling of the cold chain failure 
If a temperature 8℃ and above is recorded in the refrigerator storing the vaccine as a cold chain 
failure, the investigators should promptly handle it in accordance with the relevant operating 
procedures as soon as possible and report to the sponsor in time. It is shown by the accelerated 
stability study that the quadrivalent influenza vaccine can be placed under 37℃ conditions for 3 
days, with trial results meeting the quality standards. Therefore, when the storage temperature of the 

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Protocol No.: PRO-QINF-3005                                                                                
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test vaccine is ＞8℃ for the first time, but the maximum temperature is ≤10℃ for less than 60 
minutes, the vaccine can continue to be used normally. Otherwise, it is required to decide to stop or 
continue using the vaccine according to the sponsor’s written/email response. 
10.5.2 Investigational vaccine receipt 
When the sponsor sends the investigational vaccine to the study site, the investigator must sign the 
vaccine receipt form. This receipt form should briefly state the information for the vaccine 
acceptance (such as complete package and normal indication of the cold chain system). 
Do not use the vaccine if the investigators find that the vaccines are is damaged or spoiled, or has 
lumpy material that cannot be shaken. Return the vaccines to the sponsor. If the cold chain system is 
destroyed or the vaccines are frozen during the transportation and storage, the vaccines cannot be 
used. They should be stored separately and marked “X” on the outer package, and assign special 
personnel in charge of them before returned to the sponsor. 
10.5.3 Investigational vaccine management 
The investigational vaccines should be stored separately, managed by specially-assigned person in 
specially-assigned locking cabinet. The storage conditions should meet the storage requirements of 
the test vaccines and accept the monitoring of the CRAs. The vaccine warehousing account will 
record the amounts of vaccines received, administered to the participants and the amount remaining 
or lost. The investigators will count all the test vaccines at the end of the trials. When the study is 
completed on-site, the remaining vaccines will be counted and returned to the sponsor. 
10.6 Clinical trial sample management 
The samples used for antibody detection shall be disposed as the medical waste by the institution 
responsible for serum testing after completing the test. The backup serum shall be temporarily kept 
by the on-site trial institution until NIFDC issues the immunogenicity test report and the correct 
verification. The backup serum may be disposed of through mutual consultation between the 
sponsor and the clinical trial institution after the conclusion of the project. The serum samples from 
this clinical trial shall be used exclusively for antibody detection in immunogenicity evaluation. 
Any use of the samples for other research purposes shall obtain the consent of the subject's guardian 
and the approval of the EC. 
10.7 Clinical trial data storage 
The clinical trial data shall be kept in accordance with the requirements of GCP; the sponsor, the 
responsible institution and the on-site trial institution shall keep the clinical trial data for at least 5 
years after the trials. 
10.8 Completion criteria for the clinical trials 
(1) The samples have been sent to the corresponding testing institution and the test reports have 
been issued;  
(2) All the participants have completed the required fellow-up, and the original clinical trial data 
and documents have been transferred to the archivist for archiving;  
(3) The remaining amount of the test vaccines is accurate and handed over to the sponsor; and  

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Protocol No.: PRO-QINF-3005                                                                                
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(4) The statistical analysis report and clinical summary report meet the requirements of the sponsor. 
11. Ethical approval 
11.1 Review and approval 
This clinical trial protocol should be approved by the EC. The Principal Investigator should submit 
the clinical trial protocol and all necessary additional documentation to EC. Upon approval by the 
EC, the investigators should provide the sponsor with a certificate of approval from EC. 
11.2 Implementation of on-site supervision 
During the whole process of the trial, EC will monitor whether there are any ethical problems that 
the participants are damaged and whether the participants are treated and compensated for the 
damage and receive the corresponding measures, and will evaluate the risk degree that the 
participants are exposed to. 
11.2.1 Informed consent 
Ensure that the method of participant selection and the relevant information provided to the 
participants are complete and understandable and ensure that the informed consent is obtained by 
appropriate means. Throughout the trials, EC will periodically review the progress of the trials and 
assess the risks and benefits of the participants. 
11.2.2 Benefits 
After receiving the trial vaccine, participants may produce protective antibodies to prevent infection 
by the corresponding types of influenza viruses, with the specific outcome depending on the 
participants' immune response to the vaccine. 
11.2.3 Potential risk and risk minimization 
If an adverse event is determined to be related to the vaccination (post-vaccination abscess and rash 
at the vaccination site), the participant will be treated promptly in accordance with the relevant 
regulations. If a life-threatening incident occurs, the participant will be immediately escorted to the 
hospital for treatment and reported.  
Under strict supervision, the trained and experienced medical staff will perform the vaccination and 
the venous blood collection in accordance with the prescribed procedures to minimize the injury 
and pain (including pain and rare local infection at the venipuncture site) caused by the vaccination 
and blood collection. 
In addition, due to individual differences in immunity, some participants may not acquire immune 
protection after vaccination. 
11.2.4 Participant protection 
The clinical trials are conducted at the county/city center for disease control and prevention that are 
eligible for vaccination. The sponsor will evaluate the trial site in strict accordance with GCP 
requirements prior to the start of the trials. The environmental facilities of the trial site should meet 
the requirements of the “Guidelines for Quality Management of Vaccine Clinical Trials (Trial)”. 
Emergency plan for the participant damage and emergency should be made at the trial site. 
Qualified and experienced doctors and nurses with relevant qualifications will be assigned in the 

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Protocol No.: PRO-QINF-3005                                                                                
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medical examination rooms and blood collection rooms in order to strictly adhere to the 
selection/exclusion criteria and successfully finish the blood collection. The emergency rooms are 
equipped with appropriate first aid facilities, first aid equipment, first aid medicines and the 
emergency physicians with the appropriate qualifications and abilities. When any adverse events 
occur on the trial site, the participant will be treated in the emergency room in a timely manner; and 
in need of emergency hospitalization, after the condition becomes stable treated on-site, the 
participant shall be transported to the agreed hospital by the ambulance equipped with necessary 
first-aid facilities and drugs. The trial site and the local comprehensive hospitals at the county level 
and above will sign the green channel agreement. Agreement shall be notified to hospital that the 
participants should receive timely medical treatment during their enrollment, including the 
personnel responsibilities, contact phone and ambulance route etc, to guarantee the emergency 
treatment and measures in case of occurrence of any adverse events, so as to ensure the effect 
communication between the participants and the investigators to swift report and treatment of any 
adverse events. If any participant needs to be hospitalized for emergency treatment upon the 
occurrence of any serious adverse event, the agreed hospital shall be able to provide green channel 
medical services, including medical treatment and hospitalization to ensure the participants to get 
medical treatment in time. The investigators should follow the progress of the events and complete 
the investigation records until the end of SAE. 
11.3 Confidentiality 
Ensure that the participant's personal confidentiality is not to be disclosed, including during the 
trials and the biometric sampling collection as well as including in any reports and publication. The 
records of the trial samples shall only include the participant code, sample number, sample 
collection time and the testing index. Access to the relevant electronic or written copies is strictly 
limited to the Principal Investigator. 
12. Revision of clinical trial protocol 
After the sponsor and the investigator have signed the clinical trial protocol, if any protocol is to be 
revised, all of them should be re-signed and dated by the Principal Investigator and the sponsor, 
followed by the original protocol.  
All the revised protocols should be notified to EC and approved by EC before implementation. At 
the same time when the protocol is being revised, it should be pointed out whether it is necessary to 
modify the informed consent and electronic CRF, etc. 
13. Data disclosure and publication 
After the completion of this clinical trial, if their results need to be disclosed and/or published, the 
positive results will be disclosed and/or published together with the negative results. 
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Protocol No.: PRO-QINF-3005                                                                                
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Protocol No.: PRO-QINF-3005                                                                                
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