A Clinical Trial on Sequential Immunization of Recombinant COVID-19 Vaccine (CHO Cell, NVSI-06-09) and Inactivated COVID-19 Vaccine (Vero Cell)

Study Overview
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Brief Summary
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A total of 516 healthy subjects aged 18 years and above who have been vaccinated with 2 doses/3 doses of inactivated COVID-19 vaccine, will be enrolled, and randomly assigned to experimental group and control group in a 1:1 ratio, with 258 subjects in each sequential group.

Official Title
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A Randomized, Controlled Clinical Trial on Sequential Immunization of Recombinant COVID-19 Vaccine (CHO Cell, NVSI-06-09) and Inactivated COVID-19 Vaccine (Vero Cell) in Population Aged 18 Years and Above

Conditions
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COVID-19

Intervention / Treatment
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* Biological: Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-09)
* Biological: Inactivated COVID-19 vaccine (Vero cells)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: population aged 18 years and above; Judged by the investigator that the health condition is well after inquiry and physical examination; Vaccinated with 2 or 3 doses of inactivated COVID-19 vaccine (Vero Cell vaccine) 6 months prior to study screening and according to product insert; Female participants who are not pregnant or nursing or at the time of enrolment (confirmed via negative urine pregnancy test), and do not have plans to become pregnant within the first 6 months after enrollment. Effective contraceptive measures have been taken within 2 weeks before study inclusion and initiation; Be able and willing to provide written informed consent to participate in the study and complete all study requirements according to the study protocol; Exclusion Criteria: COVID-19 infection positive patients (including suspected or asymptomatic cases); Have a history of SARS and MERS infection; Have been vaccinated by any COVID-19 Vaccines other than Vero Cell vaccine； Have an axillary temperature 37.3 (forehead temperature 37.8℃℃); Have had previous allergic reactions to vaccination (such as acute allergic reactions, urticaria, eczema, dyspnea, angioneurotic oedema or abdominal pain) or allergy to known components of COVID-19 vaccine; History of thrombocytopenia or other coagulation disorders; Patients with known immunological impairment or immunocompromised. Received whole blood, blood products, plasma and/or immunoglobulin therapy within 3 months before study enrollment Have known or suspected severe illness such as respiratory illness, acute infection or active attacks of chronic illness, liver and kidney disease, severe diabetes mellitus, malignant tumour, infectious or allergic skin disease, human immunodeficiency virus (HIV) infection (test report available); Diagnosed with serious cardiovascular diseases such as cardiopulmonary failure, drug-uncontrolled hypertension (Systolic blood pressure 160 mmHg and/or diastolic blood pressure 95 mmHg). Received live attenuated vaccines within 1 month before study enrollment; Received inactivated vaccines within 14 days before study enrollment; Received other investigational drugs within 6 months before study enrollment; Other vaccination-related contraindications considered by investigators.

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: NVSI-06-09 Sequential Immunization Group<br>the subjects who have been vaccinated with 2 doses/3 doses of inactivated COVID-19 vaccine (Vero cell) for ≥6 months | Biological: Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-09)<br>* Intramuscular injection of Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-09) in the deltoid muscle of the upper arm<br>|
| Active Comparator: Inactivated Vaccine Sequential Immunization Group<br>the subjects who have been vaccinated with 2 doses/3 doses of inactivated COVID-19 vaccine (Vero cell) for ≥6 months | Biological: Inactivated COVID-19 vaccine (Vero cells)<br>* Biological/Vaccine: Inactivated COVID-19 vaccine (Vero cells) Intramuscular injection of Inactivated COVID-19 vaccine (Vero cells) in the deltoid muscle of the upper arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GMT (Omicron) of anti-SARS-CoV-2 neutralizing antibody in adults ≥18 years of age |  | 14 days after sequential immunization of one booster dose | 
| the 4-fold rise rate of anti-omicron neutralizing antibody in adults ≥18 years of age |  | 14 days after a single dose of the booster vaccine | 
| The incidence rate of any adverse reactions/events |  | within 30 minutes after vaccination | 
| The incidence severity of any adverse reactions/events |  | within 30 minutes after vaccination | 
| The incidence rate of solicited adverse reactions/events |  | within 0-7 days after vaccination | 
| The incidence severity of solicited adverse reactions/events |  | within 0-7 days after vaccination | 
| The incidence rate of solicited adverse reactions/events |  | within 8-30 days after vaccination | 
| The incidence severity of solicited adverse reactions/events |  | within 8-30 days after immunization | 
| The incidence of SAE observed |  | up to 12 months after full course of immunization | 
| The incidence of AESI observed |  | up to 12 months after full course of immunization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 4-fold rise rate of anti-omicron neutralizing antibody in adults ≥18 years of age |  | 28 days after sequential immunization of one booster dose | 
| GMT of anti-omicron neutralizing antibody in adults ≥18 years of age |  | 28 days after sequential immunization of one booster dose | 
| 4-fold rise rate of anti-SARS-CoV-2 neutralizing antibody in adults ≥18 years of age |  | 28 days after sequential immunization of one booster dose | 
| GMT of anti-omicron IgG antibody in adults ≥18 years of age |  | before booster vaccination and 28 days after a single dose of the booster vaccine | 
| 4-fold rise rate of anti-omicron IgG antibody in adults ≥18 years of age |  | before booster vaccination and 28 days after a single dose of the booster vaccine | 
| proportions of neutralizing antibody tittered 1: 16, 1: 32 and 1: 64 of anti-SARS-CoV-2 IgG antibody in adults ≥18 years of age |  | before booster vaccination and 28 days after a single dose of the booster vaccine | 
| GMI of anti-omicron IgG antibody in adults ≥18 years of age |  | before booster vaccination and 28 days after a single dose of the booster vaccine | 
| GMTs of anti-omicron neutralizing antibody |  | 3 months, 6 months, 9 months and 12 months after sequential immunization | 
| IgG antibody of anti-omicron neutralizing antibody |  | 3 months, 6 months, 9 months and 12 months after sequential immunization | 
| the proportions of neutralizing antibody titered 1: 16, 1: 32 and 1: 64 |  | 3 months, 6 months, 9 months and 12 months after sequential immunization | 

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