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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19
• Intervention / Treatment: Biological: COVID-19 Vaccine (Vero Cell), Inactivated; Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 4200
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changde, Hunan, China, 415200
      • Linli County Center for Disease Control and Prevention
    • Changning, Hunan, China, 421500
      • Changning Center for Disease Control and Prevention
    • Changsha, Hunan, China
      • Ningxiang Center for Disease Control and Prevention
    • Changsha, Hunan, China
      • Outpatient Department of Hunan Provincial Center For Disease Control And Prevention
    • Loudi, Hunan, China
      • Loudi Public Health Hospital
    • Xiangtan, Hunan, China
      • Xiangtan Center For Disease Control And Prevention
    • Xiangxi, Hunan, China
      • Luxi County Center for Disease Control and Prevention
    • Xiangxiang, Hunan, China
      • Xiangxiang Center for Disease Control and Prevention
    • Yueyang, Hunan, China
      • Huarong County Center for Disease Control and Prevention
    • Zhuzhou, Hunan, China, 412300
      • You County Center for Disease Control and Prevention

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

28

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; 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; intramuscular injection in the deltoid muscle
Active Comparator: A2：one dose, 18-59 years old, from 3 months to 6 months after 2 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Experimental: A3：one dose, 18-59 years old, from 6 months to 12 months after 2 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Active Comparator: A4：one dose, 18-59 years old, from 6 months to 12 months after 2 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Experimental: B1：one dose, 18-59 years old, from 3 months to 6 months after 3 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Active Comparator: B2：one dose, 18-59 years old, from 3 months to 6 months after 3 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Experimental: B3：one dose, 18-59 years old, from 6 months to 12 months after 3 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Active Comparator: B4：one dose, 18-59 years old, from 6 months to 12 months after 3 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Experimental: C1：two doses, 18-59 years old, from 3 months to 6 months after 2 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Active Comparator: C2：two doses, 18-59 years old, from 3 months to 6 months after 2 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Experimental: C3：two doses, 18-59 years old, from 6 months to 12 months after 2 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Active Comparator: C4：two doses, 18-59 years old, from 6 months to 12 months after 2 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Experimental: C5：two doses, 18-59 years old, more than 12 months after 2 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Active Comparator: C6：two doses, 18-59 years old, more than 12 months after 2 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Experimental: D1：two doses, 60 years old and above, from 3 months to 6 months after 2 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Active Comparator: D2：two doses, 60 years old and above, from 3 months to 6 months after 2 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Experimental: D3：two doses, 60 years old and above, from 6 months to 12 months after 2 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Active Comparator: D4：two doses, 60 years old and above, from 6 months to 12 months after 2 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Experimental: E1：two doses, 18-59 years old, from 3 months to 6 months after 3 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Active Comparator: E2：two doses, 18-59 years old, from 3 months to 6 months after 3 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Experimental: E3：two doses, 18-59 years old, from 6 months to 12 months after 3 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Active Comparator: E4：two doses, 18-59 years old, from 6 months to 12 months after 3 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Experimental: E5：two doses, 18-59 years old, more than 12 months after 3 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Active Comparator: E6：two doses, 18-59 years old, more than 12 months after 3 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Experimental: F1：two doses, 60 years old and above, from 3 months to 6 months after 3 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Active Comparator: F2：two doses, 60 years old and above, from 3 months to 6 months after 3 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Experimental: F3：two doses, 60 years old and above, from 6 months to 12 months after 3 doses of vaccination; 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; intramuscular injection in the deltoid muscle
Active Comparator: F4：two doses, 60 years old and above, from 6 months to 12 months after 3 doses of vaccination; 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; intramuscular injection in the deltoid muscle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	Time Frame
Specific cellular immune response	within 28 days 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 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
The neutralizing antibody GMT	on 3rd month, 6th month, 9th month, and 12th month after vaccination
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

Other Outcome Measures

Outcome Measure	Time Frame
The incidence of COVID-19 cases , including severe cases and deaths accompanied by COVID-19	From 14 day after vaccination
The neutralizing antibody GMT to different variants of SARS-CoV-2	On Day 28 after vaccination
The IgG antibody lever against Omicron SARS-CoV-2	On Day 14 and Day 28 after vaccination

Collaborators and Investigators

• Sponsor: China National Biotec Group Company Limited
• Collaborators: Beijing Institute of Biological Products Co Ltd.; Hunan Provincial Center for Disease Control and Prevention

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2022
• Primary Completion (Actual): September 25, 2022
• Study Completion (Estimated): November 10, 2023

Study Registration Dates

• First Submitted: May 13, 2022
• First Submitted That Met QC Criteria: May 13, 2022
• First Posted (Actual): May 16, 2022

Study Record Updates

• Last Update Posted (Estimated): June 19, 2023
• Last Update Submitted That Met QC Criteria: June 16, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: vaccine; COVID-19; inactivated vaccine
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: CNBG-BIBP-O-2022004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No