Clinical Trial on Sequential Immunization of Recombinant COVID-19 Vaccine (CHO Cells,NVSI-06-08) and Inactivated COVID-19 Vaccine (Vero Cells) in Population Aged 18 Years and Above

Study Overview
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Brief Summary
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This is randomized, blinded and controlled design. Among the randomly selected subjects who have been vaccinated with two doses of Inactivated COVID-19 vaccine (Vero cell), based on a step-wise approach, the subjects will receive one dose of recombinant COVID-19 vaccine sequentially at different shedules of 4-6 months, 7-9 months and >9 months after two doses of vaccination, and the subjects vaccinated at different schedules will be randomly assigned to different sequential immunization groups. At the same time, each sequential immunization group will be matched with a control group with the inactivated COVID-19 vaccine (vero cells) as the booster dose.

Official Title
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A Randomized, Controlled Phase I and Sequential Study to Evaluate the Safety and Immunogenicity Following Immunization of GEN2-Recombinant COVID-19 Vaccine (CHO Cells,NVSI-06-08) and Inactivated COVID-19 Vaccine (Vero Cells) in Population Aged 18 Years and Above

Conditions
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COVID-19 Pneumonia, Coronavirus Infections

Intervention / Treatment
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* Biological: Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08)
* Biological: Inactivated COVID-19 vaccine (Vero cells)
* Biological: 3 doses Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age range: populations aged 18 years and above; Judged by the investigator that the health condition is well after inquiry and physical examination; Vaccinated with 2 doses of CNBG inactivated COVID-19 vaccine according to the product insert（sequential clinical trial group） Never vaccinated COVID-19 vaccine（safety observation group）; Female subjects 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. During the whole follow-up period of the study, be able and willing to complete the whole prescribed study plan; Self has ability to understand the study procedures, the informed consent & voluntarily sign an informed consent form and is able to comply with the requirements of the clinical study protocol. Exclusion Criteria: Confirmed cases, suspected cases or asymptomatic cases of COVID-19; With a history of SARS and MERS infection (self-report, on-site inquiry); Has vaccinated with any vaccine other than one or more doses of CNBG inactivated COVID-19 vaccine; Axillary temperature ≥ 37.3 ℃ (forehead temperature ≥ 37.8 ℃); Previous severe allergic reactions to vaccination (such as acute allergic reactions, urticaria, dyspnea, angioneurotic edema or abdominal pain) or allergy to known components of recombinant COVID-19 vaccine; Allergic to any component of the study vaccine (e.g. aluminum, histidine, etc.) Known or suspected diseases include：Severe respiratory diseases, severe liver and kidney diseases, hypertension (systolic blood pressure ≥ 150 mmHg, diastolic blood pressure ≥ 90 mmHg), diabetic complications, malignant tumors, various acute diseases or acute attacks of chronic diseases; Has been diagnosed with congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia or other autoimmune diseases; Has a history of convulsions, epilepsy, encephalopathy，long term history of alcohol and drug abuse, history of thyroidectomy, infectious diseasesor mental illness or family history（lineal）; With Congenital malformation or developmental disorder, genetic defect, severe malnutrition, etc.; Has a history of coagulation dysfunction (e.g. coagulation factors deficiency and coagulation diseases); Absence of spleen or splenectomy, functional absence of spleen caused by any condition Anti -TB (TB) treatment is under way. Patients receiving immunoenhancement or inhibitor therapy within 3 months (continuous oral or IV administration for more than 14 days); Received blood products before within 3 months before vaccination; Received other investigational drugs within 6 months before vaccination; Plan to move before the end of the study or leave the local area for a long time during the scheduled study visit Other circumstances judged by investigators that are not suitable for this clinical trial

Ages Eligible for Study
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Minimum Age: 18 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: Subject last vaccination time is within 4-6 months（sequential clinical trial group）<br>Subject have been vaccinated with two doses of Inactivated COVID-19 vaccine (Vero cell).The last vaccination time is within 4-6 months | Biological: Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08)<br>* Intramuscular injection of Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08) in the deltoid muscle of the upper arm<br>Biological: Inactivated COVID-19 vaccine (Vero cells)<br>* Intramuscular injection of Inactivated COVID-19 vaccine (Vero cells) in the deltoid muscle of the upper arm<br>|
| Experimental: Subject last vaccination time is within 7-9 months（sequential clinical trial group）<br>Subject have been vaccinated with two doses of Inactivated COVID-19 vaccine (Vero cell).The last vaccination time is within 91-180 days 7-9 months | Biological: Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08)<br>* Intramuscular injection of Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08) in the deltoid muscle of the upper arm<br>Biological: Inactivated COVID-19 vaccine (Vero cells)<br>* Intramuscular injection of Inactivated COVID-19 vaccine (Vero cells) in the deltoid muscle of the upper arm<br>|
| Experimental: Subject last vaccination time more than 9 months（sequential clinical trial group）<br>Subject have been vaccinated with two doses of Inactivated COVID-19 vaccine (Vero cell).The last vaccination time more than 9 months | Biological: Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08)<br>* Intramuscular injection of Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08) in the deltoid muscle of the upper arm<br>Biological: Inactivated COVID-19 vaccine (Vero cells)<br>* Intramuscular injection of Inactivated COVID-19 vaccine (Vero cells) in the deltoid muscle of the upper arm<br>|
| Experimental: Safety Observation Group<br>Subject have been vaccinated with three doses of Recombinant COVID-19 Vaccine (CHO Cells,NVSI-06-08) on 0，30，60 days | Biological: 3 doses Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08)<br>* Intramuscular injection of Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08) in the deltoid muscle of the upper arm on 0，30，60 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence and serverity of any adverse reactions |  | within 30 minutes after vaccination | 
| The incidence and serverity of solicited adverse events |  | within 30 minutes after vaccination | 
| The incidence and serverity of solicited adverse reactions |  | within 0-7 days after vaccination | 
| The incidence and severity of unsolicited adverse reactions |  | within 0-7 days after vaccination | 
| The incidence and serverity of solicited adverse reactions |  | within 8-30 days after vaccination | 
| The incidence and serverity of solicited adverse events |  | within 8-30 days after vaccination | 
| The incidence of SAE observed |  | after vaccination and up to 6 months after full course of immunization. | 
| The incidence of AESI observed |  | after vaccination and up to 6 months after full course of immunization | 
| GMT of subject's anti- SARS-CoV-2 neutralizing antibody |  | 15th day after vaccination | 
| GMT of subject's anti- SARS-CoV-2 neutralizing antibody |  | 30th day after vaccination | 
| Rate of 4-fold rise of anti- SARS-CoV-2 neutralizing antibody |  | 15th day after vaccination | 
| Rate of 4-fold rise of anti- SARS-CoV-2 neutralizing antibody |  | 30th day after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of GMT of subject's anti-SARS-CoV-2 IgG antibody |  | before vaccination | 
| Rate of GMT of subject's anti-SARS-CoV-2 IgG antibody |  | 30th day after the full course of vaccination | 
| Rate of 4-fold rise of anti- SARS-CoV-2 neutralizing antibody |  | before vaccination | 
| Rate of 4-fold rise of anti- SARS-CoV-2 neutralizing antibody |  | 30th day after the full course of vaccination | 
| GMI of subject's anti-SARS-CoV-2 IgG antibody |  | before vaccination | 
| GMI of subject's anti-SARS-CoV-2 IgG antibody |  | 30th day after the full course of vaccination | 
| Proportion of neutralizing antibody titer ≥ 1: 16, ≥ 1: 32 and ≥ 1: 64 |  | before vaccination | 
| Proportion of neutralizing antibody titer ≥ 1: 16, ≥ 1: 32 and ≥ 1: 64 |  | 30th day after the full course of vaccination | 
| Rate of Anti-SAR-CoR-2 neutralizing antibody | only sequential clinical trial group | the 3th month, 6th month, 12th month, 18 month and 24th month after the full course of vaccination | 
| Rate of GMT of IgG antibody | only sequential clinical trial group | the 3th month, 6th month, 12th month, 18 month and 24th month after the full course of vaccination | 
| Rate of the titer of neutralizing antibody ≥ 1: 16, ≥ 1: 32 and ≥ 1: 64 | only sequential clinical trial group | the 3th month, 6th month, 12th month, 18 month and 24th month after the full course of vaccination | 
| Rate of Anti-SAR-CoR-2 neutralizing antibody | only Safety Observation Group | the 6th month, 12th month after the full course of vaccination | 
| Rate of GMT of IgG antibody | only Safety Observation Group | the 6th month, 12th month after the full course of vaccination | 
| Rate of the titer of neutralizing antibody ≥ 1: 16, ≥ 1: 32 and ≥ 1: 64 | only Safety Observation Group | the 6th month, 12th month after the full course of vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19