A Study to Evaluate The Efficacy, Safety and Immunogenicity of Inactivated SARS-CoV-2 Vaccines (Vero Cell) in Healthy Population Aged 18 Years Old and Above (COVID-19)

Multicenter, Randomized, Double Blind, Parallel Placebo Controlled, Phase III Clinical Trial to Evaluate the Protective Efficacy, Safety and Immunogenicity of Inactivated SARS-CoV-2 Vaccines (Vero Cell) in Healthy Population Aged 18 Years Old and Above

This is a multicenter, randomized, double blind, parallel placebo controlled, phase 3 clinical trial to evaluate the protective efficacy, safety and immunogenicity of inactivated SARS-CoV-2 vaccines in healthy population 18 years old and above.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell); Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell); Biological: Placebo

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the protective efficacy, safety and immunogenicity of inactivated SARS-CoV-2 vaccines in healthy population 18 years old and above. The participants were randomized into three groups of investigational vaccine 1, investigational vaccine 2 and placebo in a 1:1:1 ratio.2 doses of the investigational vaccine or placebo are inoculated into the deltoid muscle of the either arm according to the vaccination schedule of D0 & D21 (+7 days).According to the immune durability results in Phase I/II study, and cross-neutralization assay results, a third dose (booster dose) generates a better immune response and is estimated to offer better protection, therefore, a booster dose will be given after 3 months

• Study Type: Interventional
• Enrollment (Actual): 44101
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bahrain
  • Sanabis, Bahrain
    • Bahrain International Exhibition & Convention Centre Affiliated to Salymynia Medical Complex S
• Egypt
  • Cairo, Egypt, 11835
    • Katameya Medical Center
  • Cairo, Egypt, 22311
    • Vacsera health Care facilities , MoH
• Jordan
  • Amman, Jordan
    • Prince Hamza Hospital
• United Arab Emirates
  • Abu Dhabi, United Arab Emirates, 51900
    • Sheikh Khalifa Medical City, SEHA
  • Sharjah, United Arab Emirates, 61545
    • Al Qarain Primary Health Care Centre-MOHAP

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Healthy subjects aged 18 years old and above.
2. By asking for medical history and physical examination, the investigator judged that the health condition is well.
3. 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 3 months after enrolment. Effective contraceptive measures have been taken within 2 weeks before inclusion.
4. During the whole follow-up period of the study, be able and willing to complete the whole prescribed study plan.
5. 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:

1. Confirmed acute cases of SARS-CoV-2 Infection.
2. Have a history of SARS, MERS infection (self-report, on-site inquiry).
3. Positive urine pregnancy test result.
4. Fever (body temperature > 37.0 ℃), dry cough, fatigue, nasal obstruction, runny nose, pharyngeal pain, myalgia, diarrhea, shortness of breath and dyspnea occurred within 14 days before vaccination.
5. Axillary body temperature > 37.0 ℃ before vaccination.
6. 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.
7. Has a history of convulsion, epilepsy, encephalopathy or mental illness or family history.
8. With congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc.
9. With severe liver diseases, severe kidney diseases defined as eGFR less than 60, uncontrollable hypertension (systolic blood pressure >150 mmHg, diastolic blood pressure > 90 mmHg), diabetic complications, malignant tumors, various acute diseases, or acute attack period of chronic diseases.
10. Has been diagnosed with congenital or acquired immune deficiency, HIV infection, lymphoma, leukemia or other autoimmune diseases.
11. With known or suspected diseases include acute respiratory diseases (e.g. influenza like illness, acute cough, sore throat), severe cardiovascular diseases, liver and kidney diseases, and malignant tumors.
12. Has a history of coagulation dysfunction (e.g. Coagulation factor deficiency, coagulation disease).
13. Receiving anti-TB therapy.
14. Patients receiving immunotherapy or inhibitor therapy within 3 months (continuous oral or infusion for more than 14 days).
15. Live attenuated vaccine is inoculated within 1 month before this vaccination, other vaccines are inoculated within 14 days before this vaccination.
16. Received blood products within 3 months before this vaccination
17. Received other research drugs within 6 months before this vaccination.
18. Other circumstances judged by investigators that are not suitable for this clinical trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Investigational Vaccine 1; Participants will receive 2 doses of the inactivated SARS-CoV-2 vaccine (Vero cell) manufactured by WIBP according to the immunization schedule of D0 & D21.	Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell); The inactivated SARS-CoV-2 Vaccine (Vero cell) manufactured by WIBP; Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell); The inactivated SARS-CoV-2 Vaccine (Vero cell) manufactured by BIBP
Experimental: Investigational Vaccine 2; Participants will receive 2 doses of the inactivated SARS-CoV-2 vaccine (Vero cell) manufactured by BIBP according to the immunization schedule of D0 & D21.	Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell); The inactivated SARS-CoV-2 Vaccine (Vero cell) manufactured by WIBP; Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell); The inactivated SARS-CoV-2 Vaccine (Vero cell) manufactured by BIBP
Placebo Comparator: Placebo; Participants will receive 2 doses of Placebo according to the immunization schedule of D0 & D21.	Biological: Placebo; The placebo of inactivated SARS-CoV-2 Vaccine (Vero cell) manufactured by WIBP
Experimental: Investigational Vaccine 1b; Participants will receive a booster dose of the inactivated SARS-CoV-2 vaccine (Vero cell) manufactured by WIBP after 3 months following two doses of immunization.	Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell); The inactivated SARS-CoV-2 Vaccine (Vero cell) manufactured by WIBP; Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell); The inactivated SARS-CoV-2 Vaccine (Vero cell) manufactured by BIBP
Experimental: Investigational Vaccine 2b; Participants will receive a booster dose of the inactivated SARS-CoV-2 vaccine (Vero cell) manufactured by BIBP after 3 months following two doses of immunization.	Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell); The inactivated SARS-CoV-2 Vaccine (Vero cell) manufactured by WIBP; Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell); The inactivated SARS-CoV-2 Vaccine (Vero cell) manufactured by BIBP
Placebo Comparator: Placebo-b; Participants will receive a booster dose of Placebo after 3 months following two doses of immunization.	Biological: Placebo; The placebo of inactivated SARS-CoV-2 Vaccine (Vero cell) manufactured by WIBP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The incidence of COVID-19 cases after two-doses of vaccination	From14 days after the second dose to 6 month after the second dose
The incidence of COVID-19 cases after the booster dose of immunization	From 14 days after the booster dose

Secondary Outcome Measures

Outcome Measure	Time Frame
The incidence of any adverse reactions/events	28 days after each immunization
The incidence of severe cases of COVID-19 and deaths accompanied by COVID-19 after two-doses of vaccination	From 14 day after the second dose to 6 month after the second dose
The incidence of severe cases of COVID-19 and deaths accompanied by COVID-19 after two-doses of vaccination	From 14 day after the booster dose
The incidence of serious adverse events (SAE)	From the beginning of the first dose to 12 months after the second immunization
The Geometric Mean Titer (GMT) of anti-SARS-CoV-2 neutralizing antibody	14 days after full course of immunization
The four-fold increase rate of anti-SARS-CoV-2 neutralizing antibody	14 days after full course of immunization
The Geometric Mean Fold Rise (GMFR) of anti-SARS-CoV-2 neutralizing antibody	14 days after full course of immunization
The Geometric Mean Titer (GMT) of anti-SARS-CoV-2 neutralizing antibody	28 days, 3rd month, 6th month, 9th month, and 12th month after 2 doses of immunization
The 4-fold increase rate of anti-SARS-CoV-2 neutralizing antibody	28 days, 3rd month, 6th month, 9th month, and 12th month after 2 doses of immunization
The Geometric Mean Fold Rise (GMFR) of anti-SARS-CoV-2 neutralizing antibody	28 days, 3rd month, 6th month, 9th month, and 12th month after 2 doses of immunization
The Geometric Mean Titer (GMT) of anti-SARS-CoV-2 neutralizing antibody	14 days, 28 days and 6th month after the booster dose
The 4-fold increase rate of anti-SARS-CoV-2 neutralizing antibody	14 days, 28 days and 6th month after the booster dose
The Geometric Mean Fold Rise (GMFR) of anti-SARS-CoV-2 neutralizing antibody	14 days, 28 days and 6th month after the booster dose

Other Outcome Measures

Outcome Measure	Time Frame
the anti-SARS-CoV-2 neutralizing antibody protective level against COVID-19	14 days after 2 doses of vaccination
The occurrence of ADE	From the beginning of the first dose to 12 months after the second immunization

Collaborators and Investigators

• Sponsor: China National Biotec Group Company Limited
• Collaborators: Beijing Institute of Biological Products Co Ltd.; Wuhan Institute of Biological Products Co., Ltd; Abu Dhabi Health Services Company; G42 Healthcare company
• Investigators: Study Director: Walid A Zaher, MD, MSc,PhD, G42 Healthcare company

Publications and helpful links

General Publications

• Luan N, Li T, Wang Y, Cao H, Yin X, Lin K, Liu C. Th2-Oriented Immune Serum After SARS-CoV-2 Vaccination Does Not Enhance Infection In Vitro. Front Immunol. 2022 Apr 8;13:882856. doi: 10.3389/fimmu.2022.882856. eCollection 2022.
• Al Kaabi N, Zhang Y, Xia S, Yang Y, Al Qahtani MM, Abdulrazzaq N, Al Nusair M, Hassany M, Jawad JS, Abdalla J, Hussein SE, Al Mazrouei SK, Al Karam M, Li X, Yang X, Wang W, Lai B, Chen W, Huang S, Wang Q, Yang T, Liu Y, Ma R, Hussain ZM, Khan T, Saifuddin Fasihuddin M, You W, Xie Z, Zhao Y, Jiang Z, Zhao G, Zhang Y, Mahmoud S, ElTantawy I, Xiao P, Koshy A, Zaher WA, Wang H, Duan K, Pan A, Yang X. Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults: A Randomized Clinical Trial. JAMA. 2021 Jul 6;326(1):35-45. doi: 10.1001/jama.2021.8565.

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2020
• Primary Completion (Actual): June 16, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: August 3, 2020
• First Submitted That Met QC Criteria: August 10, 2020
• First Posted (Actual): August 12, 2020

Study Record Updates

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

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Coronavirus; SARS-CoV-2 Vaccine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: CNBG2020003SQ

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