Safety and Immunogenicity Study of Inactivated Vaccine for Prophylaxis 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 Ⅰ/Ⅱ 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 safety and immunogenicity of the experimental vaccine in healthy adults aged 18 59 Years.

Detailed Description
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This study is a randomized, double-blinded, single-center, placebo-controlled phase Ⅰ/Ⅱ clinical trial in adults aged 18 59 years. The purpose of this study is to evaluate the immunogenicity and safety of the experimental SARS-CoV-2 inactivated vaccine. The experimental vaccine and placebo were both manufactured by Sinovac Research & Development Co., Ltd. A total of 744 subjects will be enrolled, with 144 at phase Ⅰ, and 600 at phase Ⅱ. All of participants in phase Ⅰ will be assigned to receive two doses of experimental vaccine or placebo on the schedule of day 0,14 or day 0,28.300 participants in phase Ⅱ will be assigned to receive two doses of experimental vaccine or placebo on the schedule of day 0,14 or day 0,28 and one dose of booster immunization will be given 6 months after primary immunization of day 0,14 or day 0,28.The other 300 participants in phase Ⅱ will be assigned to receive three doses of experimental vaccine or placebo on the schedule of day 0,14,42 or 0,28,56 .

Official Title
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A Randomized, Double-Blinded, Placebo-Controlled, Phase Ⅰ/Ⅱ Clinical Trial, to Evaluate the Safety and Immunogenicity of the SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18 59 Years

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 emergency vaccination schedule
* Biological: Two doses of high dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule
* Biological: Two doses of placebo at the emergency vaccination schedule
* Biological: Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule
* Biological: Two doses of high dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule
* Biological: Two doses of placebo at the routine vaccination schedule
* Biological: Three doses of medium dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule
* Biological: Three doses of high dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule
* Biological: Three doses of placebo at the emergency vaccination schedule
* Biological: Three doses of medium dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule
* Biological: Three doses of high dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule
* Biological: Three doses of placebo at the routine vaccination schedule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults aged 18-59 years; Proven legal identity; Participants should be capable of understanding the informed consent form, and such form should be signed prior to enrolment ; Exclusion Criteria: Travel history / residence history of Wuhan city and surrounding areas, or other communities with case reports within 14 days; History of contact with a SARS-CoV-2 infection (positive in nucleic acid test) within 14 days; Have contacted patients with fever or respiratory symptoms from Wuhan and surrounding areas, or from communities with case reports within 14 days; Have contacted patients with fever or respiratory symptoms from Wuhan and surrounding areas, or from communities with case reports within 14 days; Self-reported history of SARS; Self-reported history of new coronavirus infection; Positive in serum antibodies (IgG or IgM) screening of COVID-19; Positive in nasopharyngeal swabs or anal swabs through RT-PCR; Women who are breastfeeding, pregnant or planning to become pregnant during the study period; BMI≥35 kg/m2; History of asthma, history of allergy to the vaccine or vaccine components, or serious adverse reactions to the vaccine, such as urticaria, dyspnea, and angioedema; Congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc.; Autoimmune disease or immunodeficiency / immunosuppression; Suffering from severe chronic diseases, severe cardiovascular diseases, hypertension and diabetes that cannot be controlled by drugs, liver and kidney diseases, malignant tumors, etc.; Severe neurological disease (epilepsy, convulsions or convulsions) or mental illness; Thyroid disease or history of thyroidectomy, spleenlessness, functional spleenlessness, spleenlessness 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; Abnormal laboratory test results in the physical examination such as clinically significant abnormal hematology and biochemistry beyond the reference value range (only applicable to Phase I clinical trials); History of alcohol or drug abuse; Receipt of blood products within 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; Attacks of acute diseases or 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 participating in the clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Emergency schedule & Two doses of medium dosage vaccine<br>24 participants in phase Ⅰand 60 participants in phase Ⅱ will receive two doses of medium dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule,and 60 participants in phase Ⅱ will receive one dose of booster immunization with medium dosage vaccine 6 months after the emergency schedule | Biological: Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule<br>* Two doses of medium dosage (600SU/0.5ml) experimental vaccine at the schedule of day 0,14,and one dose of booster immunization with medium dosage (600SU/0.5ml) experimental vaccine 6 months after the schedule of day 0,14 in phaseⅡ.<br>|
| Experimental: Emergency schedule & Two doses of high dosage vaccine<br>24 participants in phase Ⅰand 60 participants in phase Ⅱ will receive two doses of high dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule,and 60 participants in phase Ⅱ will receive one dose of booster immunization with high dosage vaccine 6 months after the emergency schedule | Biological: Two doses of high dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule<br>* Two doses of high dosage (1200 SU/0.5ml) experimental vaccine at the schedule of day 0,14 and one dose of booster immunization with high dosage (1200SU/0.5ml) experimental vaccine 6 months after the schedule of day 0,14 in phaseⅡ.<br>|
| Placebo Comparator: Emergency schedule &Two doses of placebo<br>24 participants in phase Ⅰand 30 participants in phase Ⅱ will receive two doses of placebo at the emergency vaccination schedule,and 30 participants in phase Ⅱ will receive one dose of booster immunization with placebo 6 months after the emergency schedule | Biological: Two doses of placebo at the emergency vaccination schedule<br>* Two doses of placebo at the schedule of day 0,14 and one dose of booster immunization with placebo 6 months after the schedule of day 0,14 in phaseⅡ.<br>|
| Experimental: Routine schedule & Two doses of medium dosage vaccine<br>24 participants in phase Ⅰand 60 participants in phase Ⅱ will receive two doses of medium dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule,and 60 participants in phase Ⅱ will receive one dose of booster immunization with medium dosage vaccine 6 months after the routine schedule | Biological: Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule<br>* Two doses of medium dosage (600SU/0.5ml) experimental vaccine at the schedule of day 0,28 and one dose of booster immunization with medium dosage (600SU/0.5ml) experimental vaccine 6 months after the schedule of day 0,28 in phaseⅡ.<br>|
| Experimental: Routine schedule &Two doses of high dosage vaccine<br>24 participants in phase Ⅰand 60 participants in phase Ⅱ will receive two doses of high dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule,and 60 participants in phase Ⅱ will receive one dose of booster immunization with high dosage vaccine 6 months after the routine schedule | Biological: Two doses of high dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule<br>* Two doses of high dosage (1200 SU/0.5ml) experimental vaccine at the schedule of day 0,28 and one dose of booster immunization with high dosage (1200SU/0.5ml) experimental vaccine 6 months after the schedule of day 0,28 in phaseⅡ<br>|
| Placebo Comparator: Routine schedule & Two doses of placebo<br>24 participants in phase Ⅰand 30 participants in phase Ⅱ will receive two doses of placebo at the routine vaccination schedule,and 30 participants in phase Ⅱ will receive one dose of booster immunization with placebo 6 months after the routine schedule | Biological: Two doses of placebo at the routine vaccination schedule<br>* Two doses of placebo at the schedule of day 0,28 and one dose of booster immunization with placebo 6 months after the schedule of day 0,28 in phaseⅡ.<br>|
| Experimental: Emergency schedule & Three doses of medium dosage vaccine<br>60 participants in phase Ⅱ will receive three doses of medium dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule | Biological: Three doses of medium dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule<br>* Three doses of medium dosage (600SU/0.5ml) experimental vaccine at the schedule of day 0,14,42<br>|
| Experimental: Emergency schedule & Three doses of high dosage vaccine<br>60 participants in phase Ⅱ will receive three doses of high dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule | Biological: Three doses of high dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule<br>* Three doses of high dosage (1200 SU/0.5ml) experimental vaccine at the schedule of day 0,14,42<br>|
| Placebo Comparator: Emergency schedule &Three doses of placebo<br>30 participants in phase Ⅱ will receive three doses of placebo at the emergency vaccination schedule | Biological: Three doses of placebo at the emergency vaccination schedule<br>* Three doses of placebo at the schedule of day 0,14,42<br>|
| Experimental: Routine schedule & Three doses of medium dosage vaccine<br>60 participants in phase Ⅱ will receive three doses of medium dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule | Biological: Three doses of medium dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule<br>* Three doses of medium dosage (600SU/0.5ml) experimental vaccine at the schedule of day 0,28,56<br>|
| Experimental: Routine schedule &Three doses of high dosage vaccine<br>60 participants in phase Ⅱ will receive three doses of high dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule | Biological: Three doses of high dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule<br>* Three doses of high dosage (1200 SU/0.5ml) experimental vaccine at the schedule of day 0,28,56<br>|
| Placebo Comparator: Routine schedule &Three doses of placebo<br>30 participants in phase Ⅱ will receive three doses of placebo at the routine vaccination schedule | Biological: Three doses of placebo at the routine vaccination schedule<br>* Three doses of placebo at the schedule of day 0,28,56<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety indexes of adverse reactions | Incidence of adverse reactions occured from Day 0 to Day 28 after each dose | From Day 0 to Day 28 after each dose | 
| Immunogenicity indexes of neutralizing-antibody seroconversion rates | The seroconversion rate of neutralizing antibodies 14 days (emergency schedule)/28 days (routine schedule) after the two-dose vaccination. | The 14th day /the 28th day after two doses of vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety indexes of adverse reactions | Incidence of adverse reactions 7 days after each dose of vaccination | 7 days after each dose of vaccination | 
| Safety indexes of Incidence of abnormal laboratory index | Incidence of abnormal laboratory index (blood routine test, blood chemistry test,and urine routine test) on the 3th day after each dose of vaccination in phase Ⅰ | On the 3th day after each dose of vaccination in phase Ⅰ | 
| Safety indexes of serious adverse events (SAEs） | Incidence of SAEs from the beginning of the vaccination to 6 months post the whole-schedule vaccination | From the beginning of the vaccination to 6 months post the whole-schedule vaccination | 
| Immunogenicity indexes of the seropositive rate, GMT, and GMI of neutralizing antibodies | The seropositive rate, GMT, and GMI of neutralizing antibodies 14 days (emergency schedule)/28 days (routine schedule) after two-dose vaccination | 14 days (emergency schedule)/28 days (routine schedule) after two-dose vaccination | 
| Immunogenicity indexes of the seroconversion rate, seropositive rate, GMT and GMI of neutralizing antibodies | The seroconversion rate, seropositive rate, GMT and GMI of neutralizing antibodies 28 days after the two doses (emergency schedule) | 28 days after the two doses (emergency schedule) | 
| Immunogenicity indexes of the seroconversion rate, seropositive rate, GMT, and GMI in Phase Ⅱ | Phase Ⅱ:The seroconversion rate, seropositive rate, GMT, and GMI 28 days after the third dose（only for days 0,14,42 and days 0,28,56 schedule） | 28 days after the third dose （only for days 0,14,42 and days 0,28,56 schedule） | 
| Immunogenicity indexes of the seropositivity rate, GMT, and GMI in Phase Ⅱ | Phase Ⅱ:The seropositivity rate, GMT, and GMI 14 day (emergency schedule)/28 days (routine schedule) after the booster dose （only for days 0,14 and days 0,28 schedule） | 14 day (emergency schedule)/28 days (routine schedule) after the booster dose （only for days 0,14 and days 0,28 schedule） | 
| Immunogenicity indexes of the seroconversion rate, seropositive rate, GMT, and GMI in Phase Ⅰ | Phase Ⅰ:The seroconversion rate, seropositive rate, GMT, and GMI 7/14/21 days after the first dose vaccination (emergency schedule) | 7/14/21 days after the first dose vaccination (emergency schedule) | 
| Immunogenicity indexes of the seroconversion rate, seropositive rate, GMT, and GMI in Phase Ⅰ | Phase Ⅰ:The seroconversion rate, seropositive rate, GMT, and GMI 28/35/42 days after the first dose vaccination (routine schedules) | 28/35/42 days after the first dose vaccination (routine schedules) | 
| Immunogenicity indexes of the seropositive rate of IgG, IgM antibodies | Phase Ⅰ:The seropositive rate of IgG, IgM antibodies 7/14/21/28/42 days after the first dose vaccination (emergency schedule) | 7/14/21/28/42 days after the first dose vaccination (emergency schedule) | 
| Immunogenicity indexes of the seropositive rate of IgG,IgM antibodies | Phase Ⅰ: The seropositive rate of IgG,IgM antibodies 28/35/42/56 days after the first dose vaccination (routine schedule) | 28/35/42/56 days after the first dose vaccination (routine schedule) |