A PhaseⅡ Study to Evaluate the Safety and Immunogenicity of COVID-19 Vaccine

Study Overview
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Brief Summary
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To evaluate the immunogenicity and safety of a COVID-19 mRNA vaccine (ZSVG-02-O) in a healthy population aged 18 years and older.

Detailed Description
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This study uses a randomized, blinded and controlled design, with age stratification of 18-59 years and ≥60 years , including the test vaccine at different doses (30 μg and 60 μg) and an active control vaccine. A total of 980 subjects will be enrolled in this study. 490 subjects aged 18-59 years will be randomly assigned to cohort A1 (test vaccine dose 1), A2 (test vaccine dose 2) and A3 (control vaccine) for the 2-dose regimen (0,28-day) and to cohort A4 (test vaccine dose 1), A5 (test vaccine dose 2) and A6 (active control) for the 1-dose regimen in a ratio of 3:3:1:3:3:1. Another 490 subjects aged 60 years or older will be randomized to cohort B1 (test vaccine dose 1), B2 (test vaccine dose 2) and B3 (active control) for the 2-dose regimen (0,28-day), and cohort B4 (test vaccine dose 1), B5 (test vaccine dose 2) and B6 (control vaccine) for the 1-dose regimen in a ratio of 3:3:1:3:3:1.

Official Title
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A Randomized, Blinded, Controlled Phase II Clinical Trial to Evaluate the Immunogenicity and Safety of a COVID-19 mRNA Vaccine (ZSVG-02-O) in a Healthy Population 18 Years of Age and Older

Conditions
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SARS-CoV-2 Infection

Intervention / Treatment
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* Biological: COVID-19 mRNA Vaccine (ZSVG-02-O)
* Biological: COVID-19 mRNA Vaccine (ZSVG-02-O)
* Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female subjects aged ≥18 years of age; Subjects who are in good physical condition as judged by the investigator based on medical history, physical examination and clinical laboratory tests; Subjects who have not been previously vaccinated with a Covid-19 vaccine or who have received the last dose (total dose ≤ 3 doses) of a Covid-19 vaccine at least 6 months ago; Subjects who have not been previously infected with Covid-19, or whose nucleic acid or antigen test has turned negative for more than 3 months after previous Covid-19 infection; Subjects are able to understand the study procedures, have provide written informed consent, and are able to comply with the requirements of the clinical study protocol. Exclusion criteria Axillary temperature ≥37.3°C; Positive polymerase chain reaction (PCR) test results within the last 48 hours; Women of childbearing potential with a positive urine pregnancy test result, or who are pregnant or breastfeeding, or who have not used effective contraception within 2 weeks prior to enrolment, or women and men who plan to have children within 12 months after full immunisation; History of epilepsy, convulsions or seizures, psychosis or family history of psychosis; Have a history of severe allergy to any medication or vaccination (e.g. acute allergic reaction, urticaria, skin eczema, dyspnoea, angioneurotic oedema, or abdominal pain) or allergy to known components of a Covid-19 vaccine; Have a history of hospital-diagnosed thrombocytopenia or other coagulation disorders; Have a history of hospital-diagnosed known immunological impairment or hypofunction; Subjects who have received whole blood, plasma or immunoglobulin therapy within 3 months; Known or suspected concomitant serious diseases, including: respiratory diseases, acute infections or active chronic diseases, liver and kidney diseases, severe diabetes, malignant tumours, infectious or allergic skin diseases, and HIV infection (with test report); Have serious cardiovascular diseases, cardiopulmonary failure, hypertension that cannot be controlled by medication (systolic blood pressure ≥ 140mmHg and/or diastolic blood pressure ≥ 90mmHg on physical examination); Received live attenuated vaccine within 1 month prior to vaccination or other vaccines within 14 days prior to vaccination; Participation in a clinical trial of another drug within 3 months prior to the first dose of vaccine or planning to participate in a clinical trial of another drug during the study period; Any other conditions that the investigator considers inappropriate for participation in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Test vaccine dose 1, 2 dose<br> | Biological: COVID-19 mRNA Vaccine (ZSVG-02-O)<br>* 30 μg<br>|
| Experimental: Test vaccine dose 2, 2 dose<br> | Biological: COVID-19 mRNA Vaccine (ZSVG-02-O)<br>* 60 μg<br>|
| Active Comparator: Active Comparator, 2 dose<br> | Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated<br>* COVILO<br>|
| Experimental: Test vaccine dose 1, 1 dose<br> | Biological: COVID-19 mRNA Vaccine (ZSVG-02-O)<br>* 30 μg<br>|
| Experimental: Test vaccine dose 2, 1 dose<br> | Biological: COVID-19 mRNA Vaccine (ZSVG-02-O)<br>* 60 μg<br>|
| Active Comparator: Active Comparator,1 dose<br> | Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated<br>* COVILO<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric mean titre (GMT) and 4-fold increasing rate of neutralizing antibodies (NAbs) against SARS-CoV-2 on 28 days after full vaccination | Geometric mean titre (GMT) and 4-fold increasing rate of neutralizing antibodies (NAbs) against SARS-CoV-2 on 28 days after full vaccination | 28 days after full immunisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GMT and 4-fold increasing rate of NAbs against SARS-CoV-2 on 14 days after full vaccination | GMT and 4-fold increasing rate of NAbs against SARS-CoV-2 on 14 days after full vaccination | 14 days after full immunisation | 
| GMT and 4-fold increasing rate of NAbs against SARS-CoV-2 on 7 days after the first immunisation | GMT and 4-fold increasing rate of NAbs against SARS-CoV-2 on 7 days after the first immunisation | 7 days after the first immunisation | 
| Proportion of NAbs against SARS-CoV-2 titres≥1:16, ≥1:32 and ≥1:64 on 14 and 28 days after full immunisation | Proportion of NAbs against SARS-CoV-2 titres≥1:16, ≥1:32 and ≥1:64 on 14 and 28 days after full immunisation | 14 days and 28 days after full immunisation | 
| GMT, 4-fold increasing rate and ratio of antibody titres ≥1:16, ≥1:32 and ≥1:64 for NAbs against SARS-CoV-2 on 90 and 180 days after full immunisation | GMT, 4-fold increasing rate and ratio of antibody titres ≥1:16, ≥1:32 and ≥1:64 for NAbs against SARS-CoV-2 on 90 and 180 days after full immunisation | 90 days and 180 days after full immunisation | 
| Incidence and severity of adverse event (AE) within 30 minutes of each dose of vaccination | Incidence and severity of AE within 30 minutes of each dose of vaccination | From the start of each immunisation until 30 minutes after each immunisation | 
| Incidence and severity of adverse reactions/events 0-14 days after each dose of vaccination | Incidence and severity of adverse reactions/events 0-14 days after each dose of vaccination | Day 0 Day 14 after each immunisation | 
| Incidence and severity of adverse reactions/events 15-28 days after each dose of vaccination | Incidence and severity of adverse reactions/events 15-28 days after each dose of vaccination | Day 15 Day 28 after each immunisation | 
| Incidence of serious adverse event (SAE) from the start of vaccination to 12 months after full vaccination | Incidence of SAE from the start of vaccination to 12 months after full vaccination | From the first dose of immunisation to 12 months after full immunisation |