Safety and Immunogenicity Study of Booster Vaccination With Medium-dosage or High-dosage SARS-CoV-2 Inactivated Vaccine for Prevention of COVID-19

Study Overview
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Brief Summary
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This is a randomized, double-blinded, phase ⅠV clinical trial of SARS-CoV-2 inactivated vaccine manufactured by manufactured by Sinovac Research & Development Co., Ltd. The purpose of this study is to evaluate the safety and immunogenicity of booster vaccination with high-dosage SARS-CoV-2 vaccine in populations who have received two-dose Coronavac with 2nd dose vaccinated more than 6 month.

Detailed Description
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This study a randomized, double-blinded, phase ⅠV clinical trial of SARS-CoV-2 inactivated vaccine .The purpose of this study is to evaluate the safety and immunogenicity of booster vaccination with high-dosage SARS-CoV-2 vaccine in populations who have received two-dose Coronavac with 2nd dose vaccinated more than 6 month.A total of 1200 subjects who have received two-dose Coronavac with 2nd dose vaccinated more than 6 month will be enrolled.All of subjects will be randomly divided into two groups in a 1:1 ratio .Subjects in experimental group will receive high-dosage SARS-CoV-2 inactivated vaccine.Subjects in control group will receive medium-dosage SARS-CoV-2 inactivated vaccine .

Official Title
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A Randomized, Double-Blinded Clinical Trial to Evaluate Additional Dose of Medium-dosage or High-dosage SARS-CoV-2 Inactivated Vaccine in Healthy Individuals Previously Vaccinated With CoronaVac

Conditions
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COVID-19

Intervention / Treatment
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* Biological: High-dosage SARS-CoV-2 vaccine
* Biological: Medium-dosage SARS-CoV-2 vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged 18-59; Proven legal identity; The subjects can understand and voluntarily sign the informed consent form and be willing to complete the study in accordance with the study plan; Have received two doses of inactivated SARS-CoV-2 vaccine(CoronaVac) manufactured by Sinovac Research & Development Co., Ltd at an interval of 21 to 35 days and is currently 6-8 months (180 to 240 days) after the second dose. Exclusion Criteria: History of SARS-CoV-2 infection(laboratory confirmed); Have received three and more doses of inactivated SARS-CoV-2 vaccine; Severe adverse reactions, such as urticaria, dyspnea, and angioneurotic edema , occurred during the primary immunization; Autoimmune disease such as systemic lupus erythematosus or immunodeficiency / immunosuppression such as AIDS, post-transplant; Severe chronic diseases, severe cardiovascular diseases, hypertension and diabetes that cannot be controlled by drugs, liver or kidney diseases, malignant tumors, etc; Severe neurological disease (epilepsy, convulsions or convulsions) or mental illness; Diagnosed abnormal blood coagulation function (eg, lack of blood coagulation factors, blood coagulopathy, abnormal platelets) or obvious bruising or blood coagulation; Immunosuppressive therapy, cytotoxic therapy, inhaled corticosteroids(excluding allergic rhinitis corticosteroid spray therapy, acute noncomplicated dermatitis superficial corticosteroid therapy) in the past 6 months; History of alcohol or drug abuse; Receipt of blood products within in the past 3 months; Receipt of other investigational drugs in the past 30 days; Receipt of attenuated live vaccines in the past 14 days; Acute diseases or acute exacerbation of chronic diseases within 7 days prior to booster vaccination; Axillary temperature >37.0°C; Already pregnant or are breastfeeding, planning to get pregnant within 1months (according to subjects' self-report and urine pregnancy test results); Participated in other clinical trials prior to enrollment and during the follow-up period, or planned to participate in other clinical trials during the clinical trial period; 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
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group<br>600 participants will receive one dose of booster vaccination with high-dosage inactivated SARS-CoV-2 vaccine . | Biological: High-dosage SARS-CoV-2 vaccine<br>* SARS-CoV-2 Inactivated Vaccine 1200SU inactivated virus in 0.5 mL of aluminium hydroxide solution per injection<br>* Other names: CoronaVac;|
| Active Comparator: Control Group<br>600 participants will receive one dose of booster vaccination with medium-dosage inactivated SARS-CoV-2 vaccine . | Biological: Medium-dosage SARS-CoV-2 vaccine<br>* SARS-CoV-2 Inactivated Vaccine 600SU inactivated virus in 0.5 mL of aluminium hydroxide solution per injection<br>* Other names: CoronaVac;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity index-GMT of neutralizing antibodies（CZ02 strain） | GMT of neutralizing antibodies（CZ02 strain） 28 days after booster vaccination. | Day 28 after booster vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity index-seropositive rate of neutralizing antibodies（CZ02 strain） | The seropositive rate of neutralizing antibodies（CZ02 strain） 28 days after booster vaccination | Day 28 after booster vaccination | 
| Immunogenicity index-seroconversion rate of neutralizing antibodies（CZ02 strain） | The seroconversion rate of neutralizing antibodies（CZ02 strain） 28 days after booster vaccination | Day 28 after booster vaccination | 
| Immunogenicity index-GMI of neutralizing antibodies（CZ02 strain） | GMI of neutralizing antibodies（CZ02 strain） 28 days after booster vaccination | Day 28 after booster vaccination | 
| Immunogenicity index-seropositive rate of neutralizing antibodies（Delta Strain） | The seropositive rate of neutralizing antibodies（Delta Strain） 28 days after booster vaccination | Day 28 after booster vaccination | 
| Immunogenicity index-seroconversion rate of neutralizing antibodies（Delta Strain） | The seroconversion rate of neutralizing antibodies（Delta Strain） 28 days after booster vaccination | Day 28 after booster vaccination | 
| Immunogenicity index-GMI of neutralizing antibodies（Delta Strain） | GMI of neutralizing antibodies（Delta Strain） 28 days after booster vaccination | Day 28 after booster vaccination | 
| Immunogenicity index-seroconversion rate of neutralizing antibodies（Omicron Strain） | The seroconversion rate of neutralizing antibodies（Omicron Strain） 28 days after booster vaccination | Day 28 after booster vaccination | 
| Immunogenicity index-seropositive rate of neutralizing antibodies（Omicron Strain） | The seropositive rate of neutralizing antibodies（Omicron Strain） 28 days after booster vaccination | Day 28 after booster vaccination | 
| Immunogenicity index-GMI of neutralizing antibodies（Omicron Strain） | GMI of neutralizing antibodies（Omicron Strain） 28 days after booster vaccination | Day 28 after booster vaccination | 
| Immunogenicity index-GMT of neutralizing antibodies（Omicron Strain） | GMT of neutralizing antibodies（Omicron Strain） 28 days after booster vaccination | Day 28 after booster vaccination | 
| Immunogenicity index-GMT of neutralizing antibodies（Delta Strain） | GMT of neutralizing antibodies（Delta Strain） 28 days after booster vaccination | Day 28 after booster vaccination |