Recombinant COVID-19 Vaccine (CHO Cell, NVSI-06-09) Phase III Clinical Trial

Study Overview
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Brief Summary
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This clinical trial adopts a randomized, double-blind and placebo-controlled design. A total of 16000 participants are planned to be enrolled, of which, Cohort 1: 15000 participants vaccinated with ≥2 doses of inactivated COVID-19 vaccine for ≥6 months will be randomly administered at ratio of 1:1:1 with 1 dose of LIBP-Rec-Vaccine, BIBP-Rec-Vaccine or placebo intramuscularly to the deltoid muscle of upper arm. Cohort 2: 1000 participants vaccinated with ≥2 doses of mRNA COVID-19 vaccine for ≥6 months will be randomly administered at ratio of 1:1 with 1 dose of LIBP-Rec-Vaccine or BIBP-Rec-Vaccine intramuscularly to the deltoid muscle of upper arm.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase III Clinical Trial to Evaluate Efficacy, Safety and Immunogenicity of LIBP Recombinant COVID-19 Vaccine (CHO Cell, NVSI-06-09) and BIBP Recombinant COVID-19 Vaccine (CHO Cell, NVSI-06-09) in Healthy Population Aged 18 and Above

Conditions
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COVID-19, Coronavirus Infections

Intervention / Treatment
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* Biological: LIBP-Rec-Vaccine
* Biological: BIBP-Rec-Vaccine
* Biological: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age range: healthy population aged ≥18; Judged by the investigator that the health condition is well after inquiry and physical examination; Cohort 1: participants vaccinated with ≥2 doses of inactivated COVID-19 vaccines for ≥6 months since the last dose of vaccination; Cohort 2: participants vaccinated with ≥2 doses of mRNA COVID-19 vaccines for ≥6 months since the last dose of vaccination; Be able and willing to complete all prescribed study schedules during the whole study period; The participant himself/herself is able and willing to understand study procedures, sign the informed consent form voluntarily after informed consent and comply to requirements of the study protocol. Exclusion Criteria: Symptomatic and suspected COVID 19 infection positive ; Urine pregnancy test is positive; Women of childbearing age who have positive urine pregnancy test, who are pregnant, lactating, or women who have planned pregnancy within 6 months; Auxiliary temperature before vaccination is ≥37.3℃ (tympanic/forehead temperature ≥37.8℃); Previous allergy history of vaccine vaccination (such as acute allergic reaction, urticaria, skin eczema, dyspnea, angioneurotic edema or abdominal pain, etc.) or allergy to known components of COVID-19 vaccine; Have a history of hospital-diagnosed thrombocytopenia or other coagulation disorders; With known immunological impairment or compromised immunological function diagnosed by the hospital; Received whole blood, plasma and immunoglobulin therapy within 1 month; Known or suspected of suffering from the following diseases: acute or chronic active respiratory diseases, severe cardiovascular diseases [cardiopulmonary failure, hypertension uncontrollable by drugs (systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 95 mmHg)], acute infection, active phase of chronic disease, liver and kidney diseases, severe diabetes, malignant tumor, infectious skin diseases or severe skin allergy, HIV infection, etc. (Examination report can be provided) Received live attenuated vaccine within one month before vaccination; Received inactivated vaccine within 14 days before vaccination; Other contraindications related to vaccination that investigators believe.

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: Cohort 1 LIBP-Rec-Vaccine Group<br>Subject vaccinated with ≥2 doses of inactivated COVID-19 vaccine for ≥6 months | Biological: LIBP-Rec-Vaccine<br>* Intramuscular injection of LIBP-Rec-Vaccine in the deltoid muscle of the upper arm<br>|
| Experimental: Cohort 1 BIBP-Rec-Vaccine Group<br>Subject vaccinated with ≥2 doses of inactivated COVID-19 vaccine for ≥6 months | Biological: BIBP-Rec-Vaccine<br>* Intramuscular injection of BIBP-Rec-Vaccine in the deltoid muscle of the upper arm<br>|
| Placebo Comparator: Cohort 1 placebo control group<br>Subject vaccinated with ≥2 doses of inactivated COVID-19 vaccine for ≥6 months | Biological: placebo<br>* Intramuscular injection of placebo in the deltoid muscle of the upper arm<br>|
| Experimental: Cohort 2 LIBP-Rec-Vaccine Group<br>Subject vaccinated with ≥2 doses of mRNA COVID-19 vaccine for ≥6 months | Biological: LIBP-Rec-Vaccine<br>* Intramuscular injection of LIBP-Rec-Vaccine in the deltoid muscle of the upper arm<br>|
| Experimental: Cohort 2 BIBP-Rec-Vaccine Group<br>Subject vaccinated with ≥2 doses of mRNA COVID-19 vaccine for ≥6 months | Biological: BIBP-Rec-Vaccine<br>* Intramuscular injection of BIBP-Rec-Vaccine 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 |
| --- | --- | --- |
| Cohort 1: Efficacy of LIBP-Rec-Vaccine/ BIBP-Rec-Vaccine against COVID-19 of immunization in healthy population aged 18 and above. | Rates of cohort 1 subjects not infected with COVID-19 | 14th day after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1: Efficacy of LIBP-Rec-Vaccine /BIBP-Rec-Vaccine against COVID-19 asymptomatic infection in healthy population aged 18 and above | Rates of cohort 1 subjects who are not asymptomatic infection with COVID-19 | 14th day after vaccination | 
| Cohort 1: Efficacy of LIBP-Rec-Vaccine /BIBP-Rec-Vaccine against COVID-19 severe cases in healthy population aged 18 and above | Rates of cohort 1 subjects who are not severe cases with COVID-19 | 14th day after vaccination | 
| Cohort 1: Efficacy of LIBP-Rec-Vaccine / BIBP-Rec-Vaccine against COVID-19 related deaths in healthy population aged 18 and above. | Rates of cohort 1 subjects who are not related deaths with COVID-19 | 14th day after vaccination | 
| GMT of subject's anti-SARS-CoV-2 neutralizing antibody is non-inferior to that of Cohort 1（ LIBP-Rec-Vaccine / BIBP-Rec-Vaccine） | Cohort 2 Immunogenicity subgroup only | 14th day after vaccination | 
| GMT of subject's anti- SARS-CoV-2 neutralizing antibody | Immunogenicity subgroup only | 14th day、28th day after vaccination | 
| GMI of subject's anti- SARS-CoV-2 neutralizing antibody | Immunogenicity subgroup only | 14th day、28th day after vaccination | 
| 4-fold increase rate of subject's anti- SARS-CoV-2 neutralizing antibody | Immunogenicity subgroup only | 14th day、28th day after vaccination | 
| GMT of subject's anti- SARS-CoV-2 neutralizing antibody | Immunogenicity subgroup only | 3th month、6th month after vaccination | 
| GMI of subject's anti- SARS-CoV-2 neutralizing antibody | Immunogenicity subgroup only | 3th month、6th month after vaccination | 
| 4-fold increase rate of subject's anti- SARS-CoV-2 neutralizing antibody | Immunogenicity subgroup only | 3th month、6th month after vaccination | 
| The incidence and severity of any adverse reactions |  | within 30 minutes after vaccination | 
| The incidence and severity of solicited adverse events |  | within 30 minutes after vaccination | 
| The incidence and severity 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 severity of solicited adverse reactions |  | within 8-30 days after vaccination | 
| The incidence and severity of solicited adverse events |  | within 8-30 days after vaccination | 
| The incidence of SAE observed |  | Within 6 months of vaccination | 
| The incidence of AESI observed |  | Within 6 months of vaccination | 
| Cross-neutralizing effect of recombinant COVID-19 vaccine against different variants (prototype strain, Delta, Omicron and other potential emerging dominant circulating variants) | Immunogenicity subgroup only | 14th day after vaccination | 

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