Sequential Immunization of Two Doses of Inactivated COVID-19 Vaccine (Omicron) in Vaccinated Population Aged 18 Years and Above (COVID-19)

A Randomized, Double-Blinded, Cohort Clinical Study on Evaluating the Safety and Immunogenicity of Sequential Immunization of Two Doses of BIBP Inactivated COVID-19 Vaccine (Omicron), WIBP Inactivated COVID-19 Vaccine (Omicron) or Inactivated COVID-19 Vaccine (Prototype) in Population Aged 18 Years and Above Who Have Completed Two or Three Doses of Inactivated or mRNA Vaccine

This trial adopts a randomized, double-blind and positive control design, it is planned to recruit 1800 healthy participants who have been vaccinated with 2/3 doses of COVID-19 inactivated vaccine or mRNA vaccine for 3 months. The participants will be divided into two strata according to the types of vaccines administered, including 900 participants of COVID-19 inactivated vaccine and 900 participants of mRNA vaccine. According to the ratio of 1:1:1, each stratum was randomly assigned to three groups: sequential BIBP- COVID-19 inactivated vaccine (Omicron), WIBP-COVID-19 inactivated vaccine (Omicron) or COVID-19 inactivated vaccine (prototype strain). And according to D0, D28 immunization schedule, two doses of corresponding group vaccines are sequentially administered.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 1804
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ivan Hung, Clinical Professor; Phone Number: +852 2255 4049; Email: ivanhung@hku.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital

Participation Criteria

Eligibility Criteria

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

Description

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/3 doses of inactivated COVID-19 vaccine or mRNA vaccine for ≥ 3 months.
• Female participants who are not nursing or pregnant at the time of enrolment (negative urine pregnancy test) and have no family planning within the first 7 months after enrollment. 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 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 Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) (self-report, on-site inquiry);
• Has vaccinated with one or four doses and above COVID-19 vaccine;
• Axillary temperature ≥37.3℃ (Tympanic temperature ≥ 37.6 ℃);
• Previous allergic reactions to drug or vaccination (such as acute allergic reactions, urticaria, eczema, dyspnea, angioneurotic edema or abdominal pain) or allergy to known components of COVID-19 vaccine (self-report, onsite enquiry);
• Have a history of hospital-diagnosed thrombocytopenia or other coagulation disorders (self-report, onsite enquiry);
• With known immunological impairment or immunocompromised diagnosed by the hospital (self-report, onsite enquiry);
• Have an uncontrolled epilepsy and other progressive neurological diseases or a history of Guillain-Barre syndrome (self-report, onsite enquiry);
• Received whole blood, plasma and immunoglobulin therapy within 1 month (self-report, onsite enquiry);
• Known or suspected severe illness includes: respiratory illness, acute infection or active attacks of chronic illness, liver and kidney disease, severe diabetes mellitus, malignant tumor, infectious or allergic skin disease, Human Immunodeficiency Virus (HIV) infection (self-report, onsite enquiry, provide test report if available);
• With hospital-diagnosed serious cardiovascular diseases (cardiopulmonary failure, drug-uncontrolled hypertension (physical examination of systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg), acute attacks of chronic respiratory illness (self-report, onsite enquiry);
• Received live attenuated vaccines within 1 month before vaccination (self-report, onsite enquiry);
• Received inactivated vaccines within 14 days before vaccination (self-report, onsite enquiry);
• Participating or planning to participate in other interventional vaccine clinical trials during this study
• Other vaccination-related contraindications considered by investigators.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1: BIBP Inactivated COVID-19 vaccine (Omicron); subjects will be blinded and receive two doses of BIBP Inactivated COVID-19 vaccine (Omicron) with 28 days apart more than 3 months after 2 or 3 doses of inactivated COVID-19 vaccine	Biological: BIBP Omicron Inactivated COVID-19 vaccine (Vero Cell); intramuscular injection in the deltoid muscle
Experimental: 2: WIBP Inactivated COVID-19 vaccine (Omicron); subjects will be blinded and receive two doses of WIBP Inactivated COVID-19 vaccine (Omicron) with 28 days apart more than 3 months after 2 or 3 doses of inactivated COVID-19 vaccine	Biological: WIBP Omicron Inactivated COVID-19 vaccine (Vero Cell); intramuscular injection in the deltoid muscle
Experimental: 3：BIBP Inactivated COVID-19 vaccine (Omicron); subjects will be blinded and receive two doses of BIBP Inactivated COVID-19 vaccine (Omicron) with 28 days apart more than 3 months after 2 or 3 doses of COVID-19 mRNA vaccine	Biological: BIBP Omicron Inactivated COVID-19 vaccine (Vero Cell); intramuscular injection in the deltoid muscle
Experimental: 4: WIBP Inactivated COVID-19 vaccine (Omicron); subjects will be blinded and receive two doses of WIBP Inactivated COVID-19 vaccine (Omicron) with 28 days apart more than 3 months after 2 or 3 doses of COVID-19 mRNA vaccine	Biological: WIBP Omicron Inactivated COVID-19 vaccine (Vero Cell); intramuscular injection in the deltoid muscle
Active Comparator: 5：Inactivated COVID-19 Vaccine (prototype); subjects will be blinded and receive two doses of Inactivated COVID-19 Vaccine (prototype) with 28 days apart more than 3 months after 2 or 3 doses of inactivated COVID-19 vaccine	Biological: COVID-19 Vaccine (Vero Cell), Inactivated; intramuscular injection in the deltoid muscle
Active Comparator: 6：Inactivated COVID-19 Vaccine (prototype); subjects will be blinded and receive two doses of Inactivated COVID-19 Vaccine (prototype) with 28 days apart more than 3 months after 2 or 3 doses of COVID-19 mRNA 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 anti-omicron neutralizing antibody	28 days after sequential vaccination of 2 doses
The 4-fold rise rate of anti-omicron neutralizing antibody	28 days after sequential vaccination of 2 doses

Secondary Outcome Measures

Outcome Measure	Time Frame
The GMT of anti-omicron neutralizing antibody	14 days after sequential vaccination of 2 doses
The 4-fold rise rate of anti-omicron neutralizing antibody	14 days after sequential vaccination of 2 doses
Specific cellular immune response	within 28 days after vaccination
The GMT of anti-omicron Immunoglobulin G (IgG) antibody	28 days after sequential vaccination of 2 doses
The proportions of neutralizing antibody titer ≥ 1: 16, ≥ 1: 32 and ≥ 1: 64	28 days after sequential vaccination of 2 doses
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 1st booster dose and up to 6 months following 2nd booster dose

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

Collaborators and Investigators

• Sponsor: China National Biotec Group Company Limited
• Collaborators: The University of Hong Kong; Beijing Institute of Biological Products Co Ltd.; Wuhan Institute of Biological Products Co., Ltd
• Investigators: Principal Investigator: Ivan Hung, Clinical Professor, The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2022
• Primary Completion (Estimated): July 27, 2023
• Study Completion (Estimated): March 31, 2024

Study Registration Dates

• First Submitted: May 17, 2022
• First Submitted That Met QC Criteria: May 17, 2022
• First Posted (Actual): May 19, 2022

Study Record Updates

• Last Update Posted (Estimated): June 19, 2023
• Last Update Submitted That Met QC Criteria: June 15, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• 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-O-2022002

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
• product manufactured in and exported from the U.S.: No