Study of the Commercial Scale SARS-CoV-2 Vaccine Against the Pilot Scale Among Adults, and Bridging Study of the Immunogenicity in Elderly Against That in Adults

Study Overview
=================
Brief Summary
-----------------
This study is a randomized, double-blinded clinical Trial, to evaluate the non-inferiority of the commercial scale Inactivated SARS-CoV-2 vaccine against that of the pilot scale among adults aged 26-45 years, and the open-labelled, bridging non-inferiority of the vaccine induced immunogenicity in elderly against that in adults.

Detailed Description
-----------------
This study is a randomized, double-blinded clinical Trial, to evaluate the non-inferiority of the commercial scale Inactivated SARS-CoV-2 vaccine against that of the pilot scale among adults aged 26-45 years, and the open-labelled, bridging non-inferiority of the vaccine induced immunogenicity in elderly against that in adults. The experimental vaccine was manufactured by Sinovac Research & Development Co.,Ltd. Totally 1040 subjects，including: 130 subjects aged 18 25 years; 520 subjects aged 26 45 years, with 260 in each group; 130 subjects aged 46 59 years; 260 subjects aged ≥60 years. Subjects will be assigned to receive two doses of medium-dosage vaccine on the schedule of 0,14.

Official Title
-----------------
A Randomized, Double-Blinded Clinical Trial, to Evaluate the Non-inferiority of the Commercial Scale Inactivated SARS-CoV-2 Vaccine Against That of the Pilot Scale Among Adults Aged 26-45 Years, and the Open-labelled, Bridging Non-inferiority of the Vaccine Induced Immunogenicity in Elderly Against That in Adults

Conditions
-----------------
Covid19

Intervention / Treatment
-----------------
* Biological: Two doses of commercial scale inactivated SARS-CoV-2 vaccine at the schedule of day 0,14
* Biological: Two doses of pilot scale inactivated SARS-CoV-2 vaccine at the schedule of day 0,14
* Biological: Two doses of pilot scale inactivated SARS-CoV-2 vaccine at the schedule of day 0,14 in elderly


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy adults aged 18-59 or elderly aged ≥60 years; Proven legal identity. Exclusion Criteria: Travel/residence history of communities with reported cases within 14 days before trial; History of exposure to Novel Coronavirus infection (nucleic acid positive) within 14 days prior to the trial; Exposed to patients with fever or respiratory symptoms from communities with reported cases within 14 days prior to the trial; Two or more cases of fever and/or respiratory symptoms in a small area such as home, office, school and class within 14 days prior to the trial; History of SARS-CoV-2 infection; History of asthma, history of allergy to vaccines or vaccine ingredients, and severe adverse reactions to vaccines, such as urticaria, dyspnea, and angioneurotic edema; Congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc.; Autoimmune disease or immunodeficiency/immunosuppression; Patients with serious chronic diseases, serious cardiovascular diseases, uncontrolled hypertension and diabetes, liver and kidney diseases, malignant tumors, etc.; Serious neurological disorder (epilepsy, convulsions or convulsions) or psychosis; History of thyroid disease or thyroidectomy, absence of spleen, functional absence of spleen, and absence of spleen or splenectomy caused by any circumstance; Coagulation dysfunction (such as coagulation factor deficiency, coagulation disease, platelet abnormality) or obvious bruising or coagulation disorder diagnosed by doctors; Immunosuppressive therapy, cytotoxic therapy, inhaled corticosteroids (excluding corticosteroid spray therapy for allergic rhinitis, and surface corticosteroid therapy for acute non-complicated dermatitis) in the past 6 months; Long history of alcohol or drug abuse; Received blood products within 3 months prior to receiving the vaccine; Received other research drugs within 30 days prior to receiving the vaccine; Received live attenuated vaccine within 14 days prior to receiving the vaccine; Received subunit or inactivated vaccine within 7 days prior to receiving the vaccine; Onset of various acute or chronic diseases within 7 days prior to the study; Axillary temperature of >37.0℃ before inoculation of the vaccine; Those who are already pregnant (including a positive urine pregnancy test) or are breastfeeding, planning to become pregnant within 2 months; In the opinion of the investigator, the participants had any other factors that made them unsuitable to participate in the clinical trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aged 26-45, Commercial Scale<br>Commercial scale inactivated SARS-CoV-2 vaccine in adults aged 26-45 years. | Biological: Two doses of commercial scale inactivated SARS-CoV-2 vaccine at the schedule of day 0,14<br>* The antigen content of the commercial scale inactivated SARS-CoV-2 vaccine was 600SU/0.5ml, vaccinated in the age group 26-45.<br>|
| Experimental: Aged 18-59, Pilot Scale<br>Pilot scale inactivated SARS-CoV-2 vaccine in adults aged 18-59 years. | Biological: Two doses of pilot scale inactivated SARS-CoV-2 vaccine at the schedule of day 0,14<br>* The antigen content of the pilot scale inactivated SARS-CoV-2 vaccine was 600SU/0.5ml, vaccinated in the age group 18-59.<br>|
| Experimental: Aged ≥60, Pilot Scale<br>Pilot scale inactivated SARS-CoV-2 vaccine in elderly aged above 60 years. | Biological: Two doses of pilot scale inactivated SARS-CoV-2 vaccine at the schedule of day 0,14 in elderly<br>* The antigen content of the pilot scale inactivated SARS-CoV-2 vaccine was 600SU/0.5ml, vaccinated in the age group above 60.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity index-geometric mean titer(GMT) of neutralizing antibody | Neutralizing antibody assay will be performed using the micro-neutralization method | Day 14 after the full course vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity index-Seroconversion rate of the 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 | Day 14 after the full course vaccination | 
| Immunogenicity index-Seropositive rate of the neutralizing antibody | Neutralizing antibody assay will be performed using the micro-neutralization method. Subjects with a antibody titer ≥1:8 will defined as seropositive | Day 14 after the full course vaccination | 
| Safety index-Incidence of adverse reactions | Incidence of adverse reactions from the beginning of the vaccination to 28 days after the full course vaccination | From the beginning of the vaccination to 28 days after the full course vaccination | 
| Safety index-Incidence of serious adverse events | SAE will be collected throughout the clinical trial | From the beginning of the vaccination to 6 months after the full course vaccination |