A Immuno-bridging and Immunization Schedules Study of COVID-19 Vaccine (Vero Cell), Inactivated

Study Overview
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Brief Summary
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This trial is a randomized study to evaluate the immunogenicity of COVID-19 Vaccine (Vero Cell), Inactivated and in population aged 60 years old and 3-17 years old with different schedules compared to that in population aged 18-59 years old with 2-dose schedule. And subjects in the same age are randomly assigned to different immunization schedule groups.

Detailed Description
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This trial is a randomized study to evaluate the immunogenicity of COVID-19 Vaccine (Vero Cell), Inactivated and in population aged 60 years old and 3-17 years old with different schedules (D0,21,42, D0, 21,111,or D0,21,171)compared to that in population aged 18-59 years old with 2-dose schedule (D0,21). And subjects in the same age are randomly assigned to different immunization schedule groups.

Official Title
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A Immunobridging and Immunization Schedules Study of COVID-19 Vaccine (Vero Cell), Inactivated in Population Aged ≥ 60 Years Old and 3-17 Years Old Compared With That in Population Aged 18-59 Years Old

Conditions
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Covid19

Intervention / Treatment
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* Biological: 3-doses schedule 1 of COVID-19 Vaccine (Vero Cell), Inactivated
* Biological: 3-doses schedule 2 of COVID-19 Vaccine (Vero Cell), Inactivated
* Biological: 3-doses schedule 3 of COVID-19 Vaccine (Vero Cell), Inactivated
* Biological: 2 doses of vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 3 years and above (after enrolled, subjects will be allocated according to age). By asking for medical history and physical examination, the health condition judged by the investigators is well. Female subjects of childbearing age are not nursing or pregnant at the time of enrolment (negative urine pregnancy test) and have no family planning within the first 3 months after enrolment. Effective contraceptive measures have been taken within 2 weeks before inclusion. No vaccination history of COVID-19 vaccine before enrollment. Be able and willing to complete the whole prescribed study plan. With self-ability to understand the study procedures, the informed consent & voluntarily sign an informed consent form and be able to comply with the requirements of the protocol. Exclusion Criteria: Confirmed cases, suspected cases or asymptomatic infections of SAR-CoV-2 infection (check China Disease Prevention and Control Information System). Has a history of SARS, MERS infection (self-report, on-site inquiry). >14-year-old subjects axillary temperature ≥37.3℃, ≤14-year-old subjects axillary temperature ≥37.5℃. Previous severe allergic reactions to vaccination (such as acute allergic reactions, urticaria, dyspnea, angioneurotic edema or abdominal pain) or allergy to known ingredients of inactivated SARS-CoV-2 vaccine have occurred. With severe liver diseases, severe kidney diseases, uncontrollable hypertension (systolic blood pressure ≥160 mmHg, diastolic blood pressure ≥100 mmHg), diabetic complications, malignant tumors, various acute diseases, or acute attack period of chronic diseases. Has been diagnosed with congenital or acquired immune deficiency, HIV infection, lymphoma, leukemia or other autoimmune diseases. Has a history of convulsion, epilepsy, encephalopathy or mental illness or family history. With congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc. Has a history of coagulation dysfunction (e.g. Coagulation factor deficiency, coagulation disease). Received immunotherapy or inhibitor therapy within 3 months (continuous oral or infusion for more than 14 days). Received live attenuated vaccinewithin 1 month before this vaccination, other vaccines are inoculated within 14 days before this vaccination. Received blood products within 3 months before enrolment. Received other research drugs within 6 months before enrolment. Other circumstances judged by investigators are not suitable for this clinical trial.

Ages Eligible for Study
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Minimum Age: 3 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1 aged ≥ 71<br>300 subjects age ≥ 71 （A1）receive 3 doses of vaccine | Biological: 3-doses schedule 1 of COVID-19 Vaccine (Vero Cell), Inactivated<br>* the schedule of Day 0, 21, 42<br>|
| Experimental: A2 aged ≥ 71<br>200 subjects age ≥ 71 （A2）receive 3 doses of vaccine | Biological: 3-doses schedule 2 of COVID-19 Vaccine (Vero Cell), Inactivated<br>* the schedule of Day 0, 21, 111<br>|
| Experimental: A3 aged ≥ 71<br>200 subjects age ≥ 71 (A3) receive 3 doses of vaccine | Biological: 3-doses schedule 3 of COVID-19 Vaccine (Vero Cell), Inactivated<br>* the schedule of Day 0, 21, 171<br>|
| Experimental: B1 aged 60-70<br>300 subjects age 60-70 (B1) receive 3 doses of vaccine | Biological: 3-doses schedule 1 of COVID-19 Vaccine (Vero Cell), Inactivated<br>* the schedule of Day 0, 21, 42<br>|
| Experimental: B2 aged 60-70<br>200 subjects age 60-70 (B2) receive 3 doses of vaccine | Biological: 3-doses schedule 2 of COVID-19 Vaccine (Vero Cell), Inactivated<br>* the schedule of Day 0, 21, 111<br>|
| Experimental: B3 aged 60-70<br>200 subjects age 60-70 (B3) receive 3 doses of vaccine | Biological: 3-doses schedule 3 of COVID-19 Vaccine (Vero Cell), Inactivated<br>* the schedule of Day 0, 21, 171<br>|
| Experimental: C1 aged 18-59<br>300 subjects age 18-59 (C1) receive 3 doses of vaccine | Biological: 3-doses schedule 1 of COVID-19 Vaccine (Vero Cell), Inactivated<br>* the schedule of Day 0, 21, 42<br>|
| Experimental: C2 aged 18-59<br>200 subjects age 18-59 (C2) receive 3 doses of vaccine | Biological: 3-doses schedule 2 of COVID-19 Vaccine (Vero Cell), Inactivated<br>* the schedule of Day 0, 21, 111<br>|
| Experimental: C3 aged 18-59<br>200 subjects age 18-59 (C3) receive 3 doses of vaccine | Biological: 3-doses schedule 3 of COVID-19 Vaccine (Vero Cell), Inactivated<br>* the schedule of Day 0, 21, 171<br>|
| Experimental: C4 aged 18-59<br>300 subjects age 18-59 (C4) receive 2 doses of vaccine | Biological: 2 doses of vaccine<br>* the schedule of Day 0, 21<br>|
| Experimental: D1 aged 9-17<br>300 subjects age 9-17 (D1) receive 3 doses of vaccine | Biological: 3-doses schedule 1 of COVID-19 Vaccine (Vero Cell), Inactivated<br>* the schedule of Day 0, 21, 42<br>|
| Experimental: D2 aged 9-17<br>200 subjects age 9-17 (D2) receive 3 doses of vaccine | Biological: 3-doses schedule 2 of COVID-19 Vaccine (Vero Cell), Inactivated<br>* the schedule of Day 0, 21, 111<br>|
| Experimental: D3 aged 9-17<br>200 subjects age 9-17 （D3）receive 3 doses of vaccine | Biological: 3-doses schedule 3 of COVID-19 Vaccine (Vero Cell), Inactivated<br>* the schedule of Day 0, 21, 171<br>|
| Experimental: D4 aged 9-17<br>300 subjects age 9-17 （D4）receive 2 doses of vaccine | Biological: 2 doses of vaccine<br>* the schedule of Day 0, 21<br>|
| Experimental: E1 aged 3-8<br>300 subjects age 3-8 （E1） receive 3 doses of vaccine | Biological: 3-doses schedule 1 of COVID-19 Vaccine (Vero Cell), Inactivated<br>* the schedule of Day 0, 21, 42<br>|
| Experimental: E2 aged 3-8<br>200 subjects age 3-8 （E2）receive 3 doses of vaccine | Biological: 3-doses schedule 2 of COVID-19 Vaccine (Vero Cell), Inactivated<br>* the schedule of Day 0, 21, 111<br>|
| Experimental: E3 aged 3-8<br>200 subjects age 3-8 （E3）receive 3 doses of vaccine | Biological: 3-doses schedule 3 of COVID-19 Vaccine (Vero Cell), Inactivated<br>* the schedule of Day 0, 21, 171<br>|
| Experimental: E4 aged 3-8<br>300 subjects age 3-8 （E4）receive 2 doses of vaccine | Biological: 2 doses of vaccine<br>* the schedule of Day 0, 21<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Geometric Mean Titer (GMT) of anti-SARS-CoV-2 neutralizing antibody | Neutralizing antibody assay will be performed using the Microcytopathic assay | 14 days after the full course immunization | 
| The four-fold increase rate of anti-SARS-CoV-2 neutralizing antibody | ≥4 fold increase from baseline | 14 days after the full course immunization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Geometric Mean Titer (GMT) of anti-SARS-CoV-2 neutralizing antibody | Neutralizing antibody assay will be performed using the Microcytopathic assay | 14 days after the second dose in schedule of Day 0,21,42 | 
| The four-fold increase rate of anti-SARS-CoV-2 neutralizing antibody | ≥4 fold increase from baseline | 14 days after the second dose in schedule of Day 0,21,42 | 
| The Geometric Mean Titer (GMT) of anti-SARS-CoV-2 neutralizing antibody | Neutralizing antibody assay will be performed using the Microcytopathic assay | before the third dose in schedules of Day 0,21,111 and Day 0,21,171 | 
| The four-fold increase rate of anti-SARS-CoV-2 neutralizing antibody | ≥4 fold increase from baseline | before the third dose in schedules of Day 0,21,111 and Day 0,21,171 | 
| Immune Persistence | Neutralizing antibody assay will be performed using the Microcytopathic assay | 3 months, 6 months, 12 months after the full course immunization | 
| Safety index-Incidence of adverse reactions | collect the all the adverse events using dairy card and contact card | From the beginning of the vaccination to 28 days after the full course immunization | 
| Safety index-Incidence of serious adverse events | All SAEs will be collected | From the beginning of the vaccination to 6 months after the full course immunization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, SARS-CoV-2 Vaccine, Coronavirus