Protective Effect, Safety and Immunogenicity of Live Attenuated Varicella Vaccine in Anhui Province

Study Overview
=================
Brief Summary
-----------------
This is Phase 4 clinical trial of live attenuated varicella vaccines manufactured by Sinovac (Dalian) Vaccine Technology Co., Ltd .The purpose of this study is to evaluate the protective effect of varicella vaccine in children aged 1-12 years and the correlation between varicella antibody and protective effect,to evaluate the immunogenicity and safety of varicella vaccine in children aged 1-12 years.

Detailed Description
-----------------
This study is Phase Ⅳ clinical trial.The experimental vaccine manufactured by Sinovac(Dalian) Vaccine Technology Co., Ltd.This clinical trial consists of four parts,and A total of 45400 subjects will be enrolled. Study 1,45000 subjects including 15000 subjects aged 1-3 years with no history of varicella vaccination ,15000 subjects aged 4-6 years with a history of 1 dose of varicella vaccine,15000 subjects aged 7-12 years with a history of 1 dose of varicella vaccine will be enrolled to evaluate protective effect of varicella vaccine. There will be 7500 subjects in the experimental group and 7500 in the control group in each age group.And subjects who voluntarily receive varicella vaccine will be included in the experimental group and other subjects will be included in the control group.All subjects in the experimental group will receive one dose of varicella vaccine. Study 2,400 healthy children including 100 subjects aged 1-3 years with no history of varicella ,150 subjects aged 4-6 years(50 children with no history of varicella vaccination and 100 children with a history of one dose of varicella vaccine),150 subjects aged 7-12 years (50 children with no history of varicella vaccination and 100 children with a history of one dose of varicella vaccine),each subject will receive one or two doses (0,3 months) of varicella vaccine. Study 3,30000 subjects from study 1 will be enrolled to conduct safety observation study,all adverse events of all subjects will be collected. Study 4,Herpes fluid collected from study 1 varicella cases will be used to conduct etiological study on the pathogenic strains of varicella cases.

Official Title
-----------------
A Clinical Trial to Evaluate Protective Effect, Safety and Immunogenicity of Live Attenuated Varicella Vaccine in Children Aged 1-12 Years

Conditions
-----------------
Varicella

Intervention / Treatment
-----------------
* Biological: Live attenuated varicella vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Study 1: Inclusion criteria for a protective effect study of varicella vaccine: Healthy children aged 1-12 years without a history of varicella; The subjects and/or guardians can understand and voluntarily sign the informed consent form (For subjects aged 8 years and above, both subjects and guardians need to sign the informed consent form); Study 2: Inclusion criteria for immunogenicity and safety evaluation of varicella vaccine: Healthy children aged 1-12 years without a history of varicella; The subjects and/or guardians can understand and voluntarily sign the informed consent form (For subjects aged 8 years and above, both subjects and guardians need to sign the informed consent form); The subjects and their guardians voluntarily participate in the study and are able to follow all study procedures; Proven legal identity. Study 3: Inclusion criteria for safety evaluation of mass vaccination of varicella vaccine : Healthy children aged 1-12 years without a history of varicella; The subjects and/or guardians can understand and voluntarily sign the informed consent form (For subjects aged 8 years and above, both subjects and guardians need to sign the informed consent form); The subjects and their guardians voluntarily participate in the study and are able to follow all study procedures; Proven legal identity; Subjects'guardians can fill in adverse events using mobile apps; Study 4: Inclusion criteria for etiological study on the pathogenic strains of varicella cases: Varicella cases among study 1 enrolled subjects who signed informed consent for biological samples collection. Exclusion Criteria: Received two doses of varicella vaccine from other manufacturers(applied to study 1 exclusion criteria); Received two doses of varicella vaccine; History of severe allergic reactions to vaccines (e.g.acute anaphylaxis, angioneurotic edema, dyspnea, etc.); Any confirmed or suspected immunodeficiency disease, including human immunodeficiency virus (HIV) infection; Axillary temperature >37.0°C; Receipt of other investigational drugs in the past 30 days; Receipt of attenuated live vaccines in the past 28 days; Receipt of inactivated or subunit vaccines in the past 7 days; According to the investigator's judgment, the subject has any other factors that are not suitable for participating in the clinical trial.

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group in Protective effect study<br>22500 subjects including 7500 subjects aged 1-3 years with no history of varicella vaccination,7500 subjects aged 4-6 years with a history of 1 dose of varicella vaccine,7500 subjects aged 7-12 years with a history of 1 dose of varicella vaccine will receive one dose of varicella vaccine. | Biological: Live attenuated varicella vaccine<br>* The live attenuated varicella vaccine was manufactured by Sinovac (Dalian) Vaccine Technology Co., Ltd. Live attenuated varicella-virus in 0.5 mL injection water with sucrose,sodium glutamate,sodium chloride,potassium chloride, sodium dihydrogen phosphate, potassium dihydrogen phosphate per injection.The routine of administration is intramuscular injection into deltoid region of the lateral upper arm.<br>|
| No Intervention: Control Group in Protective effect study<br>22500 subjects including 7500 subjects aged 1-3 years with no history of varicella vaccination,7500 subjects aged 4-6 years with a history of 1 dose of varicella vaccine,7500 subjects aged 7-12 years with a history of 1 dose of varicella vaccine. | |
| Experimental: Safety group<br>30000 subjects from study 1 will be enrolled to conduct safety observation study,all adverse events of all subjects will be collected. | Biological: Live attenuated varicella vaccine<br>* The live attenuated varicella vaccine was manufactured by Sinovac (Dalian) Vaccine Technology Co., Ltd. Live attenuated varicella-virus in 0.5 mL injection water with sucrose,sodium glutamate,sodium chloride,potassium chloride, sodium dihydrogen phosphate, potassium dihydrogen phosphate per injection.The routine of administration is intramuscular injection into deltoid region of the lateral upper arm.<br>|
| Experimental: Etiological study group<br>Herpes fluid collected from varicella cases in study 1 will be used to conduct etiological study on the pathogenic strains of varicella cases. | Biological: Live attenuated varicella vaccine<br>* The live attenuated varicella vaccine was manufactured by Sinovac (Dalian) Vaccine Technology Co., Ltd. Live attenuated varicella-virus in 0.5 mL injection water with sucrose,sodium glutamate,sodium chloride,potassium chloride, sodium dihydrogen phosphate, potassium dihydrogen phosphate per injection.The routine of administration is intramuscular injection into deltoid region of the lateral upper arm.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence density | The incidence density will be calculated by the number of confirmed cases of varicella at 42 days after vaccination. | 42 days after vaccination | 
| The protection rate | The protection rate will be calculated by the number of confirmed cases of varicella at 42 days after vaccination. | 42 days after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GMT of varicella antibody | GMT of varicella antibody at 42 days after varicella vaccination. | 42 days after varicella vaccination | 
| GMI of varicella antibody | GMI of varicella antibody at 42 days after varicella vaccination. | 42 days after varicella vaccination | 
| Positive rates of varicella antibody | Positive rate of varicella antibody at 42 days after varicella vaccination. | 42 days after varicella vaccination | 
| Immunogenicity index-GMT of varicella antibody | GMT of varicella antibody at 4 months after varicella vaccination. | 4 months after varicella vaccination | 
| Immunogenicity index-GMI of varicella antibody | GMI of varicella antibody at 4 months after varicella vaccination. | 4 months after varicella vaccination | 
| Immunogenicity index- positive rates | Positive rates of varicella antibody at 4 months after varicella vaccination. | 4 months after varicella vaccination | 
| The incidence of adverse events, serious adverse events and adverse reactions | The incidence of adverse events, serious adverse events and adverse reactions at 14 days after varicella vaccination. | 14 days after varicella vaccination | 
| Incidence of adverse events, serious adverse events and adverse reactions | The incidence of adverse events, serious adverse events and adverse reactions at 42 days after varicella vaccination. | 42 days after varicella vaccination. | 
| Safety index-Incidence of adverse events, serious adverse events and adverse reactions | The incidence of adverse events, serious adverse events and adverse reactions in 3 months after varicella vaccination. | 3 months after varicella vaccination | 
| Safety index-incidence of adverse events, serious adverse events and adverse reactions | The incidence of adverse events, serious adverse events and adverse reactions in 6 months after varicella vaccination. | 6 months after varicella vaccination | 
| Safety index- incidence of adverse events, serious adverse events and adverse reactions | The incidence of adverse events, serious adverse events and adverse reactions in 9 months after varicella vaccination. | 9 months after varicella vaccination | 
| The incidence of adverse events, serious adverse events and adverse reactions | The incidence of adverse events, serious adverse events and adverse reactions in 12 months after varicella vaccination. | 12 months after varicella vaccination |