Study on Sequential Immunization of Omicron Inactivated COVID-19 Vaccine and Prototype Inactivated COVID-19 Vaccine in Population Aged 18 Years Old and Above

Study Overview
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Brief Summary
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This is a randomized, double blind, positive controlled study to evaluate the safety and immunogenicity of Omicron COVID-19 Vaccine (Vero Cell), Inactivated in population aged 18 years old and above who have been vaccinated with 2 or 3 doses of COVID-19 Vaccine (Vero Cell), Inactivated manufactured by Beijing Institute of Biological Products, Co., Ltd.

Detailed Description
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This is a randomized, double blind, positive controlled study to evaluate the safety and immunogenicity of Omicron COVID-19 Vaccine (Vero Cell), Inactivated in population aged 18 years old and above who have been vaccinated with 2 or 3 doses of COVID-19 Vaccine (Vero Cell), Inactivated manufactured by Beijing Institute of Biological Products, Co., Ltd. According to subject's age (18-59 vs 60 and above), doses of vaccination history ( 2 doses vs 3 doses), and vaccination interval, the subjects will be stratified and assigned randomly to the study groups ( Omicron inactivated COVID-19 Vaccine) or the control groups ( Prototype inactivated COVID-19 Vaccine) in a 2:1 ratio. All subjects will receive single dose or two doses of vaccine with a interval of 28 days. The occurrence of adverse events within 28 days and serious adverse events within 12 months after vaccination will be observed. The serum antibody levels, cellular immune responses will be analyzed at different time points.

Official Title
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Safety and Immunogenicity Study on Omicron Inactivated COVID-19 Vaccine and Prototype Inactivated COVID-19 Vaccine in Population Aged 18 Years Old and Above Vaccinated the Prototype Inactivated COVID-19 Vaccine

Conditions
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COVID-19

Intervention / Treatment
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* Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated
* Biological: COVID-19 Vaccine (Vero Cell), Inactivated


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects aged 18 years old and above. By asking for medical history and physical examination, the investigator judged that the health condition is well. Has been vaccinated 2 or 3 doses of inactivated COVID-19 vaccine manufactured by BIBP more than 3 months. Female subjects of childbearing age are not nursing or pregnant at the time of enrolment (negative urine pregnancy test) and have no family planning within the first 12 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. With self-ability to understand the study procedures, the informed consent & voluntarily sign an informed consent form and be able to comply with the requirements of the clinical study protocol. Exclusion Criteria: Confirmed or suspected cases of SARS-CoV-2 Infection. Has a history of SARS, MERS, SARS-CoV-2 infection (self-report, on-site inquiry). Received one dose or more than 3 doses of inactivated COVID-19 vaccine manufactured by BIBP Received COVID-19 vaccine manufactured bu other companies (include mRNA, recombinant protein vaccines, vector vaccines, inactivated vaccines, etc.) Axillary body temperature > 37.3 ℃ before vaccination Previous severe allergic reactions to vaccination (such as acute allergic reactions, urticaria, dyspnea, angioneurotic edema or abdominal pain) or allergy to known ingredients of inactivated SARS-CoV-2 vaccine have occurred (self-report, on-site inquiry). History of hospital-diagnosed thrombocytopenia or other coagulation disorder Known immunological impairment or low level with hospital diagnosis History of uncontrolled epilepsy, other progressive neurological disorders, or Guillain-Barre syndrome (self-report, on-site inquiry). Known or suspected concomitant serious diseases include: respiratory disease, acute infection or active chronic disease, liver and kidney disease, severe diabetes, malignant tumor, infection or allergic skin disease, HIV infection. Severe cardiovascular disease (cardiopulmonary failure, uncontrolled hypertension, etc.) diagnosed by the hospital, active chronic respiratory disease Received live attenuated vaccine within 1 month before enrollment. Received other vaccines within 14 days before enrollment. Be participating in or plan to participate in other vaccine clinical trials during this study. Contraindications related to vaccination as considered by other 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1：one dose, 18-59 years old, from 3 months to 6 months after 2 doses of vaccination<br>subjects aged 18-59 years old will be blinded and receive one dose from 3 months to 6 months after 2 doses of inactivated COVID-19 vaccine | Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Active Comparator: A2：one dose, 18-59 years old, from 3 months to 6 months after 2 doses of vaccination<br>subjects aged 18-59 years old will be blinded and receive one dose from 3 months to 6 months after 2 doses of inactivated COVID-19 vaccine | Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Experimental: A3：one dose, 18-59 years old, from 6 months to 12 months after 2 doses of vaccination<br>subjects aged 18-59 years old will be blinded and receive one dose from 6 months to 12 months after 2 doses of inactivated COVID-19 vaccine | Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Active Comparator: A4：one dose, 18-59 years old, from 6 months to 12 months after 2 doses of vaccination<br>subjects aged 18-59 years old will be blinded and receive one dose from 6 months to 12 months after 2 doses of inactivated COVID-19 vaccine | Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Experimental: B1：one dose, 18-59 years old, from 3 months to 6 months after 3 doses of vaccination<br>subjects aged 18-59 years old will be blinded and receive one dose from 3 months to 6 months after 3 doses of inactivated COVID-19 vaccine | Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Active Comparator: B2：one dose, 18-59 years old, from 3 months to 6 months after 3 doses of vaccination<br>subjects aged 18-59 years old will be blinded and receive one dose from 3 months to 6 months after 3 doses of inactivated COVID-19 vaccine | Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Experimental: B3：one dose, 18-59 years old, from 6 months to 12 months after 3 doses of vaccination<br>subjects aged 18-59 years old will be blinded and receive one dose from 6 months to 12 months after 3 doses of inactivated COVID-19 vaccine | Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Active Comparator: B4：one dose, 18-59 years old, from 6 months to 12 months after 3 doses of vaccination<br>subjects aged 18-59 years old will be blinded and receive one dose from 6 months to 12 months after 3 doses of inactivated COVID-19 vaccine | Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Experimental: C1：two doses, 18-59 years old, from 3 months to 6 months after 2 doses of vaccination<br>subjects aged 18-59 years old will be blinded and receive two doses of vaccine with 28 days apart from 3 months to 6 months after 2 doses of inactivated COVID-19 vaccine | Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Active Comparator: C2：two doses, 18-59 years old, from 3 months to 6 months after 2 doses of vaccination<br>subjects aged 18-59 years old will be blinded and receive two doses of vaccine with 28 days apart from 3 months to 6 months after 2 doses of inactivated COVID-19 vaccine | Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Experimental: C3：two doses, 18-59 years old, from 6 months to 12 months after 2 doses of vaccination<br>subjects aged 18-59 years old will be blinded and receive two doses of vaccine with 28 days apart from 6 months to 12 months after 2 doses of inactivated COVID-19 vaccine | Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Active Comparator: C4：two doses, 18-59 years old, from 6 months to 12 months after 2 doses of vaccination<br>subjects aged 18-59 years old will be blinded and receive two doses of vaccine with 28 days apart from 6 months to 12 months after 2 doses of inactivated COVID-19 vaccine | Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Experimental: C5：two doses, 18-59 years old, more than 12 months after 2 doses of vaccination<br>subjects aged 18-59 years old will be blinded and receive two doses of vaccine with 28 days apart more than 12 months after 2 doses of inactivated COVID-19 vaccine | Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Active Comparator: C6：two doses, 18-59 years old, more than 12 months after 2 doses of vaccination<br>subjects aged 18-59 years old will be blinded and receive two doses of vaccine with 28 days apart more than 12 months after 2 doses of inactivated COVID-19 vaccine | Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Experimental: D1：two doses, 60 years old and above, from 3 months to 6 months after 2 doses of vaccination<br>subjects aged 60 years old and above will be blinded and receive two doses of vaccine with 28 days apart from 3 months to 6 months after 2 doses of inactivated COVID-19 vaccine | Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Active Comparator: D2：two doses, 60 years old and above, from 3 months to 6 months after 2 doses of vaccination<br>subjects aged 60 years old and above will be blinded and receive two doses of vaccine with 28 days apart from 3 months to 6 months after 2 doses of inactivated COVID-19 vaccine | Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Experimental: D3：two doses, 60 years old and above, from 6 months to 12 months after 2 doses of vaccination<br>subjects aged 60 years old and above will be blinded and receive two doses of vaccine with 28 days apart from 6 months to 12 months after 2 doses of inactivated COVID-19 vaccine | Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Active Comparator: D4：two doses, 60 years old and above, from 6 months to 12 months after 2 doses of vaccination<br>subjects aged 60 years old and above will be blinded and receive two doses of vaccine with 28 days apart from 6 months to 12 months after 2 doses of inactivated COVID-19 vaccine | Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Experimental: E1：two doses, 18-59 years old, from 3 months to 6 months after 3 doses of vaccination<br>subjects aged 18-59 years old will be blinded and receive two doses of vaccine with 28 days apart from 3 months to 6 months after 3 doses of inactivated COVID-19 vaccine | Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Active Comparator: E2：two doses, 18-59 years old, from 3 months to 6 months after 3 doses of vaccination<br>subjects aged 18-59 years old will be blinded and receive two doses of vaccine with 28 days apart from 3 months to 6 months after 3 doses of inactivated COVID-19 vaccine | Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Experimental: E3：two doses, 18-59 years old, from 6 months to 12 months after 3 doses of vaccination<br>subjects aged 18-59 years old will be blinded and receive two doses of vaccine with 28 days apart from 6 months to 12 months after 3 doses of inactivated COVID-19 vaccine | Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Active Comparator: E4：two doses, 18-59 years old, from 6 months to 12 months after 3 doses of vaccination<br>subjects aged 18-59 years old will be blinded and receive two doses of vaccine with 28 days apart from 6 months to 12 months after 3 doses of inactivated COVID-19 vaccine | Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Experimental: E5：two doses, 18-59 years old, more than 12 months after 3 doses of vaccination<br>subjects aged 18-59 years old will be blinded and receive two doses of vaccine with 28 days apart more than 12 months after 3 doses of inactivated COVID-19 vaccine | Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Active Comparator: E6：two doses, 18-59 years old, more than 12 months after 3 doses of vaccination<br>subjects aged 18-59 years old will be blinded and receive two doses of vaccine with 28 days apart more than 12 months after 3 doses of inactivated COVID-19 vaccine | Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Experimental: F1：two doses, 60 years old and above, from 3 months to 6 months after 3 doses of vaccination<br>subjects aged 60 years old and above will be blinded and receive two doses of vaccine with 28 days apart from 3 months to 6 months after 3 doses of inactivated COVID-19 vaccine | Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Active Comparator: F2：two doses, 60 years old and above, from 3 months to 6 months after 3 doses of vaccination<br>subjects aged 60 years old and above will be blinded and receive two doses of vaccine with 28 days apart from 3 months to 6 months after 3 doses of inactivated COVID-19 vaccine | Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Experimental: F3：two doses, 60 years old and above, from 6 months to 12 months after 3 doses of vaccination<br>subjects aged 60 years old and above will be blinded and receive two doses of vaccine with 28 days apart from 6 months to 12 months after 3 doses of inactivated COVID-19 vaccine | Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|
| Active Comparator: F4：two doses, 60 years old and above, from 6 months to 12 months after 3 doses of vaccination<br>subjects aged 60 years old and above will be blinded and receive two doses of vaccine with 28 days apart from 6 months to 12 months after 3 doses of inactivated COVID-19 vaccine | Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br>* intramuscular injection in the deltoid muscle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Geometric Mean Titer (GMT) of neutralizing antibody against Omicron SARS-CoV-2 |  | On Day 28 after vaccination | 
| The four-fold increase rate of neutralizing antibody against Omicron SARS-CoV-2 |  | On Day 28 after vaccination | 
| Incidence of adverse reactions |  | within 28 days after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The GMT of neutralizing antibody against Omicron SARS-CoV-2 |  | On Day 14 after vaccination | 
| The four-fold increase rate of neutralizing antibody against Omicron SARS-CoV-2 |  | On Day 14 after vaccination | 
| Specific cellular immune response |  | within 28 days after vaccination | 
| The neutralizing antibody GMT |  | on 3rd month, 6th month, 9th month, and 12th month after vaccination | 
| The proportion of subjects with neutralizing antibody GMT ≥1:16，≥1:32 and ≥1:64 |  | on 3rd month, 6th month, 9th month, and 12th month after vaccination | 
| The incidence of any adverse reactions/events |  | 28 days after each immunization | 
| The incidence of serious adverse events (SAE) and adverse events special interest (AESI) |  | From the beginning of the first dose to 12 months after vaccination | 

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