Immuno-bridging Study of Inactivated SARS-CoV-2 Vaccine in Healthy Population Aged 3-17 vs Aged 18 Years Old and Above

Study Overview
=================
Brief Summary
-----------------
This is a open label clinical trial to evaluate the efficacy, safety and immunogenicity of inactivated SARS-CoV-2 vaccines (Vero cell) in healthy people aged 3-17 years old in comparison with healthy population aged 18 years old and above

Detailed Description
-----------------
This is a open label clinical trial to evaluate the efficacy, safety and immunogenicity of inactivated SARS-CoV-2 vaccines (Vero cell) developed by Beijing Institute of Biological Products Co., Ltd in healthy people aged 3-17 years old in comparison with healthy population aged 18 years old and above. Total of 1800 healthy volunteers aged 3 years old and above will be enrolled, of whom the subjects will be divided into two groups, 3-17 years old group and 18 years old and above group with each consisting of 900 volunteers. The 3-17 years old group was further divided into three subgroups: 3-6 years old, 7-12 years old and 13-17 years old, with 300 volunteers in each subgroup. 2 doses of vaccines will be injected into the deltoid muscle of either upper arm according to the immunization schedule of D0, D21 (+7 Days). Based on interim analysis'results of the booster dose administered to adults aged 18 years old and above, a booster dose might be introduced.

Official Title
-----------------
Immunogenicity Non-inferiority Immuno-bridging Study of Inactivated SARS-CoV-2 Vaccine in Healthy Population Aged 3-17 Years Old vs Healthy Population Aged 18 Years Old and Above

Conditions
-----------------
COVID-19, COVID-19 Pneumonia

Intervention / Treatment
-----------------
* Biological: SARS-CoV-2 Vaccine (Vero Cell), Inactivated


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy subjects aged 3 years old and above Medical history and physical examination of the subject confirms the subject is in a healthy condition and is approved by the investigator Female subjects of childbearing age who 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. The subject must be able and willing to complete the whole immunization schedule of the study and be able to follow up study procedures for 6 months. With self-ability to understand the study procedures, the informed consent & voluntarily sign an informed consent/ assent form. Legal authority or parents/guardians of minors 3-17 years should sign an informed consent form and be able to comply with the requirements of the clinical study protocol. Exclusion Criteria: Confirmed acute cases of SARS-CoV-2 infection. With a medical history of SARS, MERS virus infection (self-report, on-site inquiry); Fever (axillary temperature > 37.0 ℃), dry cough, fatigue, nasal obstruction, runny nose, pharyngeal pain, myalgia, diarrhea, shortness of breath and dyspnea within 14 days before vaccination (Tympanic temperature / Temporal artery temperature >37.5 ℃); Positive urine pregnancy test result. Body temperature axillary ≥ 37.0 ℃ before vaccination（Tympanic temperature / Temporal artery temperature≥ 37.5 ℃); With previous severe allergic reactions (such as acute allergic reactions, urticaria, skin eczema, dyspnea, angioneurotic edema or abdominal pain) or allergy to known ingredients of the inactivated SARS-CoV-2 vaccine. With a medical history or a family history of convulsion, epilepsy, encephalopathy or mental illness. With congenital malformation or developmental disorder, genetic defects, severe malnutrition, etc.; With known or suspected diseases include acute respiratory diseases (e.g. influenza like illness, acute cough, sore throat), severe cardiovascular diseases, severe liver diseases, severe kidney diseases, uncontrollable hypertension (systolic blood pressure > 150 mmHg, diastolic blood pressure > 90 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; With a history of coagulation dysfunction (such as coagulation factor deficiency, coagulation disease); With a history of coagulation dysfunction (such as coagulation factor deficiency coagulation disease); Receiving anti-TB therapy. Receiving immune enhancement or inhibitor therapy within 3 months (continuous oral or IV administration for more than 14 days); Vaccinated live attenuated vaccine within 1 month before vaccination and other vaccines within 14 days before vaccination; Received blood products within 3 months before vaccination; Received other investigational drugs within 6 months before vaccination; Other circumstances judged by investigators that were not suitable for participating in this clinical trial.

Ages Eligible for Study
-----------------
Minimum Age: 3 Years

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aged 3-6 years old<br>300 subjects receive 2 dose according to the immunization schedule of D0, D21 (+7 Days). A booster dose might be introduced. | Biological: SARS-CoV-2 Vaccine (Vero Cell), Inactivated<br>* 0.5 mL per dose, containing 6.5U inactivated SARS-CoV-2 antigen<br>|
| Experimental: Aged 7-12 years old<br>300 subjects receive 2 dose according to the immunization schedule of D0, D21 (+7 Days). A booster dose might be introduced. | Biological: SARS-CoV-2 Vaccine (Vero Cell), Inactivated<br>* 0.5 mL per dose, containing 6.5U inactivated SARS-CoV-2 antigen<br>|
| Experimental: Aged 13-17 years old<br>300 subjects receive 2 dose according to the immunization schedule of D0, D21 (+7 Days). A booster dose might be introduced. | Biological: SARS-CoV-2 Vaccine (Vero Cell), Inactivated<br>* 0.5 mL per dose, containing 6.5U inactivated SARS-CoV-2 antigen<br>|
| Active Comparator: Aged ≥18 years old<br>300 subjects receive 2 dose according to the immunization schedule of D0, D21 (+7 Days). A booster dose might be introduced. | Biological: SARS-CoV-2 Vaccine (Vero Cell), Inactivated<br>* 0.5 mL per dose, containing 6.5U inactivated SARS-CoV-2 antigen<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The four-fold increase rate of anti-SARS-CoV-2 neutralizing antibody | ≥4 fold increase from baseline | 28 days after 2 dose of immunization | 
| The Geometric Mean Titer (GMT) of anti-SARS-CoV-2 neutralizing antibody | Neutralizing antibody assay will be performed using the Microcytopathic assay | 28 days after 2 dose of immunization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety index-Incidence of adverse reactions | the adverse event at injection site and systemic adverse event and other adverse events of the subjects are actively followed up and recorded in the subject diary card or follow-up calls | 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 | 
| The four-fold increase rate of anti-SARS-CoV-2 neutralizing antibody | ≥4 fold increase from baseline | 28 days after booster dose of immunization | 
| The Geometric Mean Titer (GMT) of anti-SARS-CoV-2 neutralizing antibody | Neutralizing antibody assay will be performed using the Microcytopathic assay | 28 days after booster dose of immunization | 
| The distribution of neutralizing antibody titer | The proportions of neutralizing antibody titer | 28 days after 2 dose of immunization and booster dose | 

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