Efficacy, Immunogenicity and Safety of COVID-19 Vaccine , Inactivated in Children and Adolescents

Study Overview
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Brief Summary
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This study is a global multi-center , case-driven, randomized, double-blinded, and placebo-controlled phase Ⅲ 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 efficacy of two dose of CoronaVac® against RT-PCR confirmed symptomatic COVID-19 cases in participants aged 6 months to 17 years.

Detailed Description
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This study is a global multi-center , case-driven, randomized, double-blinded, and placebo-controlled phase Ⅲ clinical trial in participants aged 6 months to 17 years.The purpose of this study is to evaluate the efficacy of two dose of CoronaVac® against RT-PCR confirmed symptomatic COVID-19 cases in participants aged 6 months to 17 years.The experimental vaccine and placebo were both manufactured by Sinovac Research & Development Co., Ltd. A total of 14,000 healthy participants aged 6 months to 17 years will be enrolled, and randomly assigned into 2 groups at a ratio of 1:1 to receive 2 doses of experimental vaccine (600SU) or placebo with an interval of 28 days.

Official Title
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A Multi-center, Randomized, Double-blind, Placebo-controlled Phase Ⅲ Clinical Trial to Evaluate the Efficacy, Immunogenicity and Safety of COVID-19 Vaccine(Vero Cell) ,Inactivated in Children and Adolescents Aged 6 Months to 17 Years

Conditions
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COVID-19

Intervention / Treatment
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* Biological: Inactivated COVID-19 Vaccine
* Biological: Controlled vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy children and adolescents aged 6 months to 17 years; The participants and/or their guardians are able to understand and sign the informed consent voluntarily (in accordance with the local regulations); Able to comply with study procedures based on the assessment of the Investigator; Female participants of childbearing potential (post-menarche girls or in accordance with the local standard of care) may be enrolled in the study if the participant fulfills all the following criteria: Has a negative pregnancy test on the day of the first dose (Day 0). Has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first dose (Day 0). Has agreed to continue adequate contraception through 3 months following the second dose (Day 28). Is not currently breastfeeding. Must be willing to provide verifiable identification (in accordance with the local regulations), has means to be contacted and to contact the investigator during the study. Exclusion Criteria: History of confirmed infection of SARS CoV-2 prior to randomization; Close contact with a confirmed COVID-19 within 14 days prior to randomization; Prior administration of an investigational coronavirus vaccine or current/planned simultaneous participation in another interventional study to prevent or treat COVID-19; Allergy to vaccines or vaccine/placebo ingredients, and serious adverse reactions to vaccines, such as urticaria, dyspnea, angioneuroedema; Personal or first-grade relative (siblings) history of multisystem inflammatory disease in children (MIS-C); Significant chronic illnesses that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion (may include, but are not limited to cardiovascular disease, liver or kidney disorders, respiratory illnesses) Significant chronic central nervous system diseases or neuromuscular disorders, psychosis or severe cognitive behavioral disorder, in the opinion of the investigator, including epilepsy, autism spectrum disorder, intellectual disabilities (excluding Down Syndrome); Acute central nervous system diseases such as encephalitis/myelitis, acute disseminating encephalomyelitis, and related disorders; History of autoimmune and/or haematological diseases (including but not limited to systemic lupus erythematosus, thyroidectomy, autoimmune thyroid disease, any form of malignant tumor, asplenia, functional asplenia, or splenectomy resulting from any condition); well controlled type I diabetes mellitus is allowed; History of bleeding disorders (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture; Immunosuppressive therapy (systemic corticoid therapy, e.g. prednisone ≥2 mg/Kg/d or ≥20 mg/day for >14 days), cytotoxic therapy (antineoplastic chemotherapy, radiation therapy), (excluding topical or aerosol corticosteroid therapy) in the past 6 months; Receipt of blood products or immunoglobulins 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 exacerbation or presentation of stable chronic diseases (including but not limited to asthma, migraine, gastrointestinal disorder, etc; Acute febrile illness with oral temperature >37.7°C or axillary temperature >37.5°C on the day of vaccination (refer to section 7.1 Delay/Discontinuation of Study Vaccination); enrollment could be considered if the fever is absent for 72 hours; Any confirmed or suspected human immunodeficiency virus (HIV) infection; Children in care or under a court order; According to the investigator's judgment, the subject has any other factors that might interfere with the results of the clinical trial or pose additional risk to the subject due to participation in the study.

Ages Eligible for Study
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Minimum Age: 6 Months
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 Group<br>subjects will receive two doses of inactivated COVID-19 vaccine on day 0 and day 28. | Biological: Inactivated COVID-19 Vaccine<br>* The inactivated COVID-19 vaccine was manufactured by Sinovac Research& Development Co., Ltd..600SU Inactivated SARS-COV-2 virus in 0·5 mL of aluminium hydroxide solution per injection<br>* Other names: CoronaVac;|
| Placebo Comparator: Control Group<br>subjects will receive two doses of placebo on day 0 and day 28. | Biological: Controlled vaccine<br>* The placebo was manufactured by Sinovac Research& Development Co., Ltd.The composition is aluminium hydroxide,The appearance of the placebo is consistent with the vaccine, which is a milky-white suspension.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy index-incidence of RT-PCR confirmed symptomatic COVID-19 cases with onset | Incidence of RT-PCR confirmed symptomatic COVID-19 cases with onset at least 14 days after the second dose | 14 days after the second dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy index-incidence of RT-PCR confirmed symptomatic COVID-19 cases with onset | Incidence of RT-PCR confirmed symptomatic COVID-19 cases with onset at least 14 days after the first dose | 14 days after the first dose | 
| Efficacy index-incidence of RT-PCR confirmed, symptomatic COVID-19 cases with onset in SARS-CoV-2 uninfected participants | Incidence of RT-PCR confirmed, symptomatic COVID-19 with onset at least 14 days after the second dose in SARS-CoV-2 uninfected (serologically or molecularly confirmed) participants at baseline | 14 days after the second dose | 
| Efficacy index-incidence of hospitalization/severe/death caused by COVID-19 with onset | Incidence of hospitalization/severe/death caused by COVID-19 with onset at least 14 days after the second dose | 14 days after the second dose | 
| Safety index-occurrence, intensity, duration, and relationship of solicited local and systemic AEs and of unsolicited AEs | Occurrence, intensity, duration, and relationship of solicited local and systemic AEs during 7 days following each dose vaccination and of unsolicited AEs during 28 days post-vaccination | During 7 days following each dose vaccination and during 28 days post-vaccination | 
| Safety index-occurrence and relationship of SAEs | Occurrence and relationship of SAEs from first dose to 12 months after the last dose | From first dose to 12 months after the last dose | 
| Safety index-occurrence and relationship of AESI | Occurrence and relationship of AESI from first dose to 12 months after the last dose | From first dose to 12 months after the last dose | 
| Immunogenicity index(subgroup)-SARS-CoV-2 neutralizing antibody titers | Analysis of SARS-CoV-2 neutralizing antibody titers by micro-cytopathic method to compare with the placebo group | From first dose to 12 months after the last dose | 
| Immunogenicity index(subgroup)-Anti-SARS-CoV-2 S | Analysis of Anti-SARS-CoV-2 S by electrochemiluminescence immunoassay to compare with the placebo group | From first dose to 12 months after the last dose |