Safety and Immunogenicity Study of Inactivated Vaccine for Prevention of COVID-19

Study Overview
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Brief Summary
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This study is a randomized, double-blinded, and placebo controlled phase 1&2 clinical trial of the SARS-CoV-2 inactivated vaccine manufactured by Sinovac Research & Development Co., Ltd. The purpose of this study is to evaluate the safety and immunogenicity of the experimental vaccine in healthy children and adolescents aged 3-17 years

Detailed Description
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This study is a randomized, double-blinded, single-center, placebo-controlled phase 1&2 clinical trial in children and adolescents aged 3-17 years. The experimental vaccine and placebo were both manufactured by Sinovac Research & Development Co., Ltd. A total of 552 subjects will be enrolled, with 72 at phase 1, and 480 at phase 2. Subjects will be assigned to receive two doses of different dosage of experimental vaccine or placebo on the schedule of day 0,28. Subjects in Phase receive the second dose 10 months or 12 months after the second dose.

Official Title
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A Randomized, Double-Blinded, Placebo-Controlled, Phase Ⅰ/Ⅱ Clinical Trial, to Evaluate the Safety and Immunogenicity of the SARS-CoV-2 Inactivated Vaccine (Vero Cell) in Healthy Population Aged 3-17 Years

Conditions
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COVID-19

Intervention / Treatment
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* Biological: Two doses of low dosage inactivated SARS-CoV-2 vaccine at the schedule of day 0,28
* Biological: Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the schedule of day 0,28
* Other: Two doses of placebo at the schedule of day 0,28


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy children and adolescents aged 3-17 years; The subject and/or guardian can understand and voluntarily sign the informed consent form (double sign required for 8-17 years old); Proven legal identity. Exclusion Criteria: Travel history / residence history of communities with case reports within 14 days; History of contact with a SARS-CoV-2 infection (positive in nucleic acid test) within 14 days; Have contacted patients with fever or respiratory symptoms from communities with case reports within 14 days; Two or more cases of fever and / or respiratory symptoms in a small contact area of volunteers, such as home, office etc. within 14 days; History of SARS-CoV-2 infection; History of asthma, history of allergy to the vaccine or vaccine components, or serious adverse reactions to the vaccine, such as urticaria, dyspnea, and angioedema; Congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc.; Autoimmune disease or immunodeficiency / immunosuppression; 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; Thyroid disease or history of thyroidectomy, spleenlessness, functional spleenlessness, spleenlessness or splenectomy resulting from any condition; 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; Physical examination has clinically significant abnormal hematology and biochemistry laboratory test results that exceed the reference value range (only applicable to phase I clinical trials): Blood routine test: white blood cell count, hemoglobin, platelet count; Detection of blood biochemical indicators: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), creatinine (CR), fasting blood glucose; Urine routine index: urine protein (PRO); 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; Receipt of inactivated or subunit vaccines in the past 7 days; Acute diseases or acute exacerbation of chronic diseases in the past 7 days; Axillary temperature >37.0°C; Already pregnant (including a positive urine pregnancy test) or are breastfeeding, planning to get pregnant within 3 months; 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: 3 Years
Maximum Age: 17 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 Vaccine-low dosage<br>low dosage inactivated SARS-CoV-2 vaccine | Biological: Two doses of low dosage inactivated SARS-CoV-2 vaccine at the schedule of day 0,28<br>* The inactivated SARS-CoV-2 vaccine was manufactured by Sinovac Research & Development Co., Ltd., with a antigen content of 300SU/0.5ml<br>|
| Experimental: Experimental Vaccine-medium dosage<br>medium dosage inactivated SARS-CoV-2 vaccine | Biological: Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the schedule of day 0,28<br>* The inactivated SARS-CoV-2 vaccine was manufactured by Sinovac Research & Development Co., Ltd., with a antigen content of 600SU/0.5ml<br>|
| Placebo Comparator: Placebo<br>No active ingredient in the placebo | Other: Two doses of placebo at the schedule of day 0,28<br>* The placebo contains no active ingredient and manufactured by Sinovac Research & Development Co., Ltd.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety index-incidence of adverse reactions | Incidence of adverse reactions after each dose vaccination. | Day 0-28 after each dose vaccination | 
| Immunogenicity index-seroconversion rates of neutralizing antibody | Neutralizing antibody assay will be performed using the micro-neutralization method. Seroconversion will be defined as a change from seronegative (<1:8) to seropositive (≥1:8), or ≥4 fold increase from baseline. | The 28th day after the second dose vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety index-incidence of serious adverse events | SAE will be collected throughout the clinical trial. | From the beginning of the vaccination to 12 months after the second dose vaccination | 
| Immunogenicity index-seropositive rates of neutralizing antibody | Neutralizing antibody assay will be performed using the micro-neutralization method, and subjects with a antibody titer ≥1:8 will defined as seropositive. | The 28th day after each dose vaccination and the 12 month after the second dose vaccination | 
| Immunogenicity index-geometric mean titer (GMT) of neutralizing antibody | Neutralizing antibody assay will be performed using the micro-neutralization method. | The 28th day after each dose vaccination and the 12 month after the second dose vaccination | 
| Immunogenicity index-geometric mean ratio (GMR) of neutralizing antibody | Neutralizing antibody assay will be performed using the micro-neutralization method. Ratio of post-vaccination titer divided by baseline titer will be calculated. | The 28th day after each dose vaccination and the 12 month after the second dose vaccination | 
| Safety index-Incidence rate of adverse reactions | Incidence rate of adverse reactions within 7 days after each dose vaccination | Within 7 days after each dose vaccination | 
| Safety index-Incidence of abnormal laboratory index | Incidence of abnormal laboratory index (blood routine test, blood chemistry test, and urine routine test) on the 3th day after each dose of vaccination in phase Ⅰ | On the 3th day after each dose of vaccination in phase Ⅰ | 
| Safety index-Incidence rate of AESIs | Incidence rate of SAEs and AESIs from the beginning of the vaccination to 12 months after the last dose vaccination | From the beginning of the vaccination to 12 months after the last dose vaccination | 
| Immunogenicity index- GMI of neutralizing antibody | GMI of neutralizing antibodies 28 days after the second dose vaccination | 28 days after the second dose vaccination | 
| Immunogenicity index-the seroconversion rate | The seroconversion rate 28 days after the first dose vaccination in phase Ⅰ | 28 days after the first dose vaccination in phase Ⅰ | 
| Immunogenicity index-the seropositive rate | Seropositive rate 28 days after the first dose vaccination in phase Ⅰ | 28 days after the first dose vaccination in phase Ⅰ | 
| Immunogenicity index-the GMT | The GMT 28 days after the first dose vaccination in phase Ⅰ | 28 days after the first dose vaccination in phase Ⅰ | 
| Immunogenicity index-the GMI | The GMI 28 days after the first dose vaccination in phase Ⅰ | 28 days after the first dose vaccination in phase Ⅰ |