Clinical trial NCT04383574: Safety and Immunogenicity Study of Inactivated Vaccine for Prevention of SARS-CoV-2 Infection(COVID-19)
Official title: A Randomized, Double-blind, Placebo-controlled Clinical Trial, to Evaluate Safety and Immunogenicity of Inactivated SARS-CoV-2 Vaccine (Vero Cell), in Healthy Elderly Aged 60 Years and Above
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: COVID-19
Lead sponsor: Sinovac Biotech Co., Ltd
Sponsor class: INDUSTRY
First posted: 2020-05-12
Enrollment: 422
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study is a randomized, double-blinded, and placebo controlled phase 1\&2 clinical trial of the SARS-CoV-2 inactivated vaccine manufactured by Sinovac Life Sciences Co. , Ltd. The purpose of this study is to evaluate the safety and immunogenicity of the experimental vaccine in healthy elderly aged 60 years and above.

Detailed description: This study is a randomized, double-blinded, single-center, placebo-controlled phase 1\&2 clinical trial in healthy elderly aged 60 years and above. The experimental vaccine and placebo were both manufactured by Sinovac Life Sciences Co. , Ltd. A total of 422 subjects will be enrolled, with 72 in phase 1 and 350 in phase 2. 72 Subjects with 36 in medium-dosage group and 36 in high-dosage group in phase 1 will receive two doses of primary immunization according to the immunization schedule of day 0, 28 and the subjects at each dosage group will be assigned in a 2:1 ratio to receive investigational vaccine or placebo respectively.All enrolled subjects will receive 1 dose of booster immunization 1 year after primary immunization.350 Subjects in phase 2 will receive two doses of primary immunization according to the immunization schedule of day 0,28,the subjects will be assigned in a ratio of 2:2:2:1 to receive the low dosage, medium dosage, high dosage vaccine, or placebo. All enrolled subjects will received 1 dose of booster immunization(the third dose ) 6 months after primary immunization.And subjects in medium-dosage group and high -dosage group will receive the second booster dose (the fourth dose) 1 year after the second dose.

Eligibility criteria: Inclusion Criteria:

* Healthy adults aged ≥60 years;
* Be able to understand and sign the informed consent voluntarily;
* Provide legal identification;

Exclusion Criteria:

* Travel / residence history of Wuhan city and surrounding areas or other communities with case reports within 14 days prior to the enrolment;
* Contact with SARS-CoV-2 infected persons (positive for nucleic acid detection) within 14 days prior to the enrolment;
* Contact patients with fever or respiratory symptoms from Wuhan city and surrounding areas, or from communities with case reports within 14 days prior to the enrolment;
* Two or more cases of fever and / or respiratory symptoms in a small contact area of subjects, such as family, office, school class or other places within 14 days prior to the enrolment;
* History of SARS;
* History of SARS-CoV-2 infection;
* History of asthma, allergy to vaccines or vaccine ingredients, and serious adverse reactions to vaccines, such as urticaria, dyspnea, angioneuroedema;
* Congenital malformation or developmental disorder, genetic defect, severe malnutrition, etc;
* Autoimmune disease or immunodeficiency / immunosuppression;
* Serious chronic disease, serious cardiovascular disease, hypertension and diabetes that cannot be controlled by drugs, hepatorenal disease, malignant tumor, etc;
* Serious nervous system disease (epilepsy, convulsion or convulsion) or psychosis;
* Thyroid disease or history of thyroidectomy, asplenia, functional asplenia, asplenia or splenectomy resulting from any condition;
* Diagnosed abnormal blood coagulation function (eg, lack of blood coagulation factors, blood coagulopathy, abnormal platelets) or obvious bruising or blood coagulation;
* Immunosuppressive therapy, cytotoxic therapy, inhaled corticosteroids (excluding allergic rhinitis corticosteroid spray therapy, acute non-complicated dermatitis superficial corticosteroid therapy) in the past 6 months;
* Long history of alcohol or drug abuse;
* Receipt of blood products in the past 3 months;
* Receipt of other investigational drugs in the past 30 days;
* Receipt of attenuated live vaccines in the past 14 days;
* Receipt of inactivated or subunit vaccines in the past 7 days;
* Acute diseases or acute exacerbation of chronic diseases in the past 7 days;
* Axillary temperature \>37.0°C;
* According to the investigator's judgment, the subject has any other factors that are not suitable for the clinical trial.

Primary outcomes:
measure: Safety index-incidence of adverse reactions
timeFrame: Day 0-28 after each dose vaccination
measure: Immunogenicity index-seroconversion rates of neutralizing antibody
timeFrame: 28 days after the second dose vaccination
Secondary outcomes:
measure: Safety index-incidence rate of adverse reactions
timeFrame: within 7 days after each dose vaccination
measure: Safety index-incidence rate of serious adverse events in phase Ⅰ
timeFrame: From the beginning of the vaccination to 6 months after the booster immunization
measure: Safety index-incidence rate of serious adverse events in phase Ⅱ
timeFrame: From the beginning of the vaccination to 12 months after the booster immunization vaccination
measure: Immunogenicity index-seropositive rate, GMT, and GMI of neutralizing antibodies
timeFrame: 28 days after the second dose vaccination
measure: Immunogenicity index-seroconversion rate, seropositive rate, GMT, and GMI in phase Ⅰ
timeFrame: 28 days after the first dose vaccination in phase Ⅰ
Other outcomes:
measure: Immunogenicity index -seropositive rate and GMT of neutralizing antibodies
timeFrame: 6 months after the second dose vaccination
measure: Immunogenicity index -seropositive rate and GMT of neutralizing antibodies in phase Ⅰ
timeFrame: 12 months after the second dose vaccination
measure: Immunogenicity index -seropositive rate, GMT, and GMI of neutralizing antibodies
timeFrame: 28 days after the booster vaccination
measure: Immunogenicity index -seropositive rate, GMT of neutralizing antibodies in phase Ⅱ
timeFrame: 7 days (or 14 days) and 28 days after the booster vaccination
measure: Immunogenicity index -seropositive rate and GMT of neutralizing antibodies
timeFrame: 6 months after the booster vaccination
measure: Immunogenicity index -seropositive rate and GMT of neutralizing antibodies in phase Ⅱ
timeFrame: 12 months after the booster vaccination
measure: Immunogenicity index-seropositive rate,GMT and GMI of neutralizing antibodies
timeFrame: 14 days after the fourth dose
measure: Immunogenicity index-Seropositive rate and GMTof neutralizing antibodies
timeFrame: 6 months after the fourth dose
Locations:
city: Renqiu
country: China
facility: Renqiu City Center for Disease Control and Prevention
state: Hebei
Study officials:
affiliation: Hubei Provincial Center for Disease Control and Prevention
name: Yuliang Zhao, Master
role: PRINCIPAL_INVESTIGATOR
References:
citation: Xin Q, Wu Q, Chen X, Han B, Chu K, Song Y, Jin H, Chen P, Lu W, Yang T, Li M, Zhao Y, Pan H, Yu H, Wang L. Six-month follow-up of a booster dose of CoronaVac in two single-centre phase 2 clinical trials. Nat Commun. 2022 Jun 3;13(1):3100. doi: 10.1038/s41467-022-30864-w.
citation: Zeng G, Wu Q, Pan H, Li M, Yang J, Wang L, Wu Z, Jiang D, Deng X, Chu K, Zheng W, Wang L, Lu W, Han B, Zhao Y, Zhu F, Yu H, Yin W. Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials. Lancet Infect Dis. 2022 Apr;22(4):483-495. doi: 10.1016/S1473-3099(21)00681-2. Epub 2021 Dec 8.
citation: Wu Z, Hu Y, Xu M, Chen Z, Yang W, Jiang Z, Li M, Jin H, Cui G, Chen P, Wang L, Zhao G, Ding Y, Zhao Y, Yin W. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis. 2021 Jun;21(6):803-812. doi: 10.1016/S1473-3099(20)30987-7. Epub 2021 Feb 3.