Safety and Immunogenicity Study of Inactivated Vaccine for Prevention of SARS-CoV-2 Infection(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 Life Sciences Co. , Ltd. The purpose of this study is to evaluate the safety and immunogenicity of the experimental vaccine in healthy elderly aged 60 years and above.

Detailed Description
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This study is a randomized, double-blinded, single-center, placebo-controlled phase 1&2 clinical trial in healthy elderly aged 60 years and above. The experimental vaccine and placebo were both manufactured by Sinovac Life Sciences Co. , Ltd. A total of 422 subjects will be enrolled, with 72 in phase 1 and 350 in phase 2. 72 Subjects with 36 in medium-dosage group and 36 in high-dosage group in phase 1 will receive two doses of primary immunization according to the immunization schedule of day 0, 28 and the subjects at each dosage group will be assigned in a 2:1 ratio to receive investigational vaccine or placebo respectively.All enrolled subjects will receive 1 dose of booster immunization 1 year after primary immunization.350 Subjects in phase 2 will receive two doses of primary immunization according to the immunization schedule of day 0,28,the subjects will be assigned in a ratio of 2:2:2:1 to receive the low dosage, medium dosage, high dosage vaccine, or placebo. All enrolled subjects will received 1 dose of booster immunization(the third dose ) 6 months after primary immunization.And subjects in medium-dosage group and high -dosage group will receive the second booster dose (the fourth dose) 1 year after the second dose.

Official Title
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A Randomized, Double-blind, Placebo-controlled Clinical Trial, to Evaluate Safety and Immunogenicity of Inactivated SARS-CoV-2 Vaccine (Vero Cell), in Healthy Elderly Aged 60 Years and Above

Conditions
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COVID-19

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults aged ≥60 years; Be able to understand and sign the informed consent voluntarily; Provide legal identification; Exclusion Criteria: Travel / residence history of Wuhan city and surrounding areas or other communities with case reports within 14 days prior to the enrolment; Contact with SARS-CoV-2 infected persons (positive for nucleic acid detection) within 14 days prior to the enrolment; Contact patients with fever or respiratory symptoms from Wuhan city and surrounding areas, or from communities with case reports within 14 days prior to the enrolment; Two or more cases of fever and / or respiratory symptoms in a small contact area of subjects, such as family, office, school class or other places within 14 days prior to the enrolment; History of SARS; History of SARS-CoV-2 infection; History of asthma, allergy to vaccines or vaccine ingredients, and serious adverse reactions to vaccines, such as urticaria, dyspnea, angioneuroedema; Congenital malformation or developmental disorder, genetic defect, severe malnutrition, etc; Autoimmune disease or immunodeficiency / immunosuppression; Serious chronic disease, serious cardiovascular disease, hypertension and diabetes that cannot be controlled by drugs, hepatorenal disease, malignant tumor, etc; Serious nervous system disease (epilepsy, convulsion or convulsion) or psychosis; Thyroid disease or history of thyroidectomy, asplenia, functional asplenia, asplenia 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 non-complicated dermatitis superficial corticosteroid therapy) in the past 6 months; Long history of alcohol or drug abuse; Receipt of blood products 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; According to the investigator's judgment, the subject has any other factors that are not suitable for the clinical trial.

Ages Eligible for Study
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Minimum Age: 60 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-medium dosage<br>24 participants in medium-dosage group in phase Ⅰ will receive two doses of primary immunization according to the immunization schedule of day 0, 28 and will receive 1 dose of booster immunization 1 year after primary immunization; 100 participants in medium-dosage group in phase Ⅱ will receive two doses of primary immunization according to the immunization schedule of day 0,28 ,1 dose of booster immunization 6 months after primary immunization(the third dose ) and the second booster dose (the fourth dose) 1 year after the second dose. | 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..Two doses of medium dosage (600SU/0.5ml) experimental vaccine at the schedule of day 0,28,and one dose of booster immunization(the third dose) with medium dosage (600SU/0.5ml) experimental vaccine 1 year after primary immunization at the schedule of day 0,28 in phaseⅠand 6 months after primary immunization at the schedule of day 0,28 in phase Ⅱ.And the second booster dose (the fourth dose) 1 year after the second dose.<br>|
| Experimental: Experimental Vaccine-high dosage<br>24 participants in high-dosage group in phase Ⅰ will receive two doses of primary immunization according to the immunization schedule of day 0, 28 and will receive 1 dose of booster immunization 1 year after primary immunization; 100 participants in high-dosage group in phase Ⅱ will receive two doses of primary immunization according to the immunization schedule of day 0,28 ,1 dose of booster immunization 6 months after primary immunization(the third dose) and the second booster dose (fourth dose) 1 year after the second dose . | Biological: Two doses of high 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..Two doses of high dosage (1200SU/0.5ml) experimental vaccine at the schedule of day 0,28,and one dose of booster immunization(the third dose) with medium dosage (1200SU/0.5ml) experimental vaccine 1 year after primary immunization at the schedule of day 0,28 in phaseⅠand 6 months after primary immunization at the schedule of day 0,28 in phase Ⅱ.And the second booster dose (the fourth dose) 1 year after the second dose.<br>|
| Placebo Comparator: Placebo<br>24 participants including 12 at medium dosage stage and 12 at high dosage in phase Ⅰ will receive two doses of placebo according to the immunization schedule of day 0, 28 and will receive 1 dose of booster immunization 1 year after primary immunization; 50 participants in phase Ⅱ will receive two doses of primary immunization according to the immunization schedule of day 0,28 and will receive 1 dose of booster immunization 6 months after primary immunization. | Biological: Two doses of placebo at the schedule of day 0,28<br>* The placebo was manufactured by Sinovac Research & Development Co., Ltd., Two doses of placebo at the schedule of day 0,28,and one dose of booster immunization with placebo 1 year after primary immunization at the schedule of day 0,28 in phaseⅠand 6 months after primary immunization at the schedule of day 0,28 in phase Ⅱ.<br>|
| Experimental: Experimental Vaccine-low dosage<br>100 participants at low dosage stage in phase Ⅱ will receive two doses of primary immunization according to the immunization schedule of day 0,28 and will receive 1 dose of booster immunization 6 months after primary immunization. | 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..Two doses of low dosage (300SU/0.5ml)experimental vaccine at the schedule of day 0,28,and one dose of booster immunization with low dosage (300SU/0.5ml) experimental vaccine 6 months after primary immunization at the schedule of day 0,28 in phase Ⅱ.<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 | The seroconversion rate of neutralizing antibody 28 days after the second dose vaccination. | 28 days after the second dose vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 rate of serious adverse events in phase Ⅰ | Incidence rate of SAEs from the beginning of the vaccination to 6 months after the booster immunization in phase Ⅰ | From the beginning of the vaccination to 6 months after the booster immunization | 
| Safety index-incidence rate of serious adverse events in phase Ⅱ | Incidence rate of SAEs from the beginning of the vaccination to 12 months after the booster immunization vaccination in phase Ⅱ | From the beginning of the vaccination to 12 months after the booster immunization vaccination | 
| Immunogenicity index-seropositive rate, GMT, and GMI of neutralizing antibodies | The seropositive rate, GMT, and GMI of neutralizing antibodies 28 days after the second dose vaccination; | 28 days after the second dose vaccination | 
| Immunogenicity index-seroconversion rate, seropositive rate, GMT, and GMI in phase Ⅰ | The seroconversion rate, seropositive rate, GMT, and GMI 28 days after the first dose vaccination in phase Ⅰ | 28 days after the first dose vaccination in phase Ⅰ |