Clinical trial NCT04510207: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Keywords: SARS-CoV-2
SARS-CoV-2 Vaccine
Coronavirus
Lead sponsor: China National Biotec Group Company Limited
Sponsor class: INDUSTRY
Collaborators: name: G42 Healthcare company
name: Abu Dhabi Health Services Company
name: Wuhan Institute of Biological Products Co., Ltd
name: Beijing Institute of Biological Products Co Ltd.
First posted: 2020-08-12
Enrollment: 44101
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: The incidence of COVID-19 cases after two-doses of vaccination
timeFrame: From14 days after the second dose to 6 month after the second dose
measure: The incidence of COVID-19 cases after the booster dose of immunization
timeFrame: From 14 days after the booster dose
Secondary outcomes:
measure: The incidence of severe cases of COVID-19 and deaths accompanied by COVID-19 after two-doses of vaccination
timeFrame: From 14 day after the second dose to 6 month after the second dose
measure: The incidence of severe cases of COVID-19 and deaths accompanied by COVID-19 after two-doses of vaccination
timeFrame: From 14 day after the booster dose
measure: The incidence of any adverse reactions/events
timeFrame: 28 days after each immunization
measure: The incidence of serious adverse events (SAE)
timeFrame: From the beginning of the first dose to 12 months after the second immunization
measure: The Geometric Mean Titer (GMT) of anti-SARS-CoV-2 neutralizing antibody
timeFrame: 14 days after full course of immunization
measure: The four-fold increase rate of anti-SARS-CoV-2 neutralizing antibody
timeFrame: 14 days after full course of immunization
measure: The Geometric Mean Fold Rise (GMFR) of anti-SARS-CoV-2 neutralizing antibody
timeFrame: 14 days after full course of immunization
measure: The Geometric Mean Titer (GMT) of anti-SARS-CoV-2 neutralizing antibody
timeFrame: 28 days, 3rd month, 6th month, 9th month, and 12th month after 2 doses of immunization
measure: The 4-fold increase rate of anti-SARS-CoV-2 neutralizing antibody
timeFrame: 28 days, 3rd month, 6th month, 9th month, and 12th month after 2 doses of immunization
measure: The Geometric Mean Fold Rise (GMFR) of anti-SARS-CoV-2 neutralizing antibody
timeFrame: 28 days, 3rd month, 6th month, 9th month, and 12th month after 2 doses of immunization
measure: The Geometric Mean Titer (GMT) of anti-SARS-CoV-2 neutralizing antibody
timeFrame: 14 days, 28 days and 6th month after the booster dose
measure: The 4-fold increase rate of anti-SARS-CoV-2 neutralizing antibody
timeFrame: 14 days, 28 days and 6th month after the booster dose
measure: The Geometric Mean Fold Rise (GMFR) of anti-SARS-CoV-2 neutralizing antibody
timeFrame: 14 days, 28 days and 6th month after the booster dose
Other outcomes:
measure: the anti-SARS-CoV-2 neutralizing antibody protective level against COVID-19
timeFrame: 14 days after 2 doses of vaccination
measure: The occurrence of ADE
timeFrame: From the beginning of the first dose to 12 months after the second immunization
Locations:
city: Sanabis
country: Bahrain
facility: Bahrain International Exhibition & Convention Centre Affiliated to Salymynia Medical Complex S
city: Cairo
country: Egypt
facility: Katameya Medical Center
city: Cairo
country: Egypt
facility: Vacsera health Care facilities , MoH
city: Amman
country: Jordan
facility: Prince Hamza Hospital
city: Abu Dhabi
country: United Arab Emirates
facility: Sheikh Khalifa Medical City, SEHA
city: Sharjah
country: United Arab Emirates
facility: Al Qarain Primary Health Care Centre-MOHAP
Study officials:
affiliation: G42 Healthcare company
name: Walid A Zaher, MD, MSc,PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.