Clinical trial NCT04352608: Safety and Immunogenicity Study of Inactivated Vaccine for Prophylaxis of SARS CoV-2 Infection (COVID-19)
Official title: A Randomized, Double-Blinded, Placebo-Controlled, Phase Ⅰ/Ⅱ Clinical Trial, to Evaluate the Safety and Immunogenicity of the SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18~59 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: COVID-19
Lead sponsor: Sinovac Biotech Co., Ltd
Sponsor class: INDUSTRY
First posted: 2020-04-20
Enrollment: 744
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: 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 Ⅰ/Ⅱ clinical trial of the SARS-CoV-2 inactivated vaccine manufactured by Sinovac Research \& Development Co., Ltd. The purpose of this study is to evaluate the safety and immunogenicity of the experimental vaccine in healthy adults aged 18\~59 Years.

Detailed description: This study is a randomized, double-blinded, single-center, placebo-controlled phase Ⅰ/Ⅱ clinical trial in adults aged 18\~59 years. The purpose of this study is to evaluate the immunogenicity and safety of the experimental SARS-CoV-2 inactivated vaccine. The experimental vaccine and placebo were both manufactured by Sinovac Research \& Development Co., Ltd. A total of 744 subjects will be enrolled, with 144 at phase Ⅰ, and 600 at phase Ⅱ. All of participants in phase Ⅰ will be assigned to receive two doses of experimental vaccine or placebo on the schedule of day 0,14 or day 0,28.300 participants in phase Ⅱ will be assigned to receive two doses of experimental vaccine or placebo on the schedule of day 0,14 or day 0,28 and one dose of booster immunization will be given 6 months after primary immunization of day 0,14 or day 0,28.The other 300 participants in phase Ⅱ will be assigned to receive three doses of experimental vaccine or placebo on the schedule of day 0,14,42 or 0,28,56 .

Eligibility criteria: Inclusion Criteria:

* Healthy adults aged 18-59 years;
* Proven legal identity;
* Participants should be capable of understanding the informed consent form, and such form should be signed prior to enrolment ;

Exclusion Criteria:

* Travel history / residence history of Wuhan city and surrounding areas, or other communities with case reports within 14 days;
* History of contact with a SARS-CoV-2 infection (positive in nucleic acid test) within 14 days;
* Have contacted patients with fever or respiratory symptoms from Wuhan and surrounding areas, or from communities with case reports within 14 days;
* Have contacted patients with fever or respiratory symptoms from Wuhan and surrounding areas, or from communities with case reports within 14 days;
* Self-reported history of SARS;
* Self-reported history of new coronavirus infection;
* Positive in serum antibodies (IgG or IgM) screening of COVID-19;
* Positive in nasopharyngeal swabs or anal swabs through RT-PCR;
* Women who are breastfeeding, pregnant or planning to become pregnant during the study period;
* BMI≥35 kg/m2;
* History of asthma, history of allergy to the vaccine or vaccine components, or serious adverse reactions to the vaccine, such as urticaria, dyspnea, and angioedema;
* Congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc.;
* Autoimmune disease or immunodeficiency / immunosuppression;
* Suffering from severe chronic diseases, severe cardiovascular diseases, hypertension and diabetes that cannot be controlled by drugs, liver and kidney diseases, malignant tumors, etc.;
* Severe neurological disease (epilepsy, convulsions or convulsions) or mental illness;
* Thyroid disease or history of thyroidectomy, spleenlessness, functional spleenlessness, spleenlessness 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;
* Abnormal laboratory test results in the physical examination such as clinically significant abnormal hematology and biochemistry beyond the reference value range (only applicable to Phase I clinical trials);
* History of alcohol or drug abuse;
* Receipt of blood products within 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;
* Attacks of acute diseases or 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 participating in the clinical trial.

Primary outcomes:
measure: Safety indexes of adverse reactions
timeFrame: From Day 0 to Day 28 after each dose
measure: Immunogenicity indexes of neutralizing-antibody seroconversion rates
timeFrame: The 14th day /the 28th day after two doses of vaccination
Secondary outcomes:
measure: Safety indexes of adverse reactions
timeFrame: 7 days after each dose of vaccination
measure: Safety indexes of Incidence of abnormal laboratory index
timeFrame: On the 3th day after each dose of vaccination in phase Ⅰ
measure: Safety indexes of serious adverse events (SAEs）
timeFrame: From the beginning of the vaccination to 6 months post the whole-schedule vaccination
measure: Immunogenicity indexes of the seropositive rate, GMT, and GMI of neutralizing antibodies
timeFrame: 14 days (emergency schedule)/28 days (routine schedule) after two-dose vaccination
measure: Immunogenicity indexes of the seroconversion rate, seropositive rate, GMT and GMI of neutralizing antibodies
timeFrame: 28 days after the two doses (emergency schedule)
measure: Immunogenicity indexes of the seroconversion rate, seropositive rate, GMT, and GMI in Phase Ⅱ
timeFrame: 28 days after the third dose （only for days 0,14,42 and days 0,28,56 schedule）
measure: Immunogenicity indexes of the seropositivity rate, GMT, and GMI in Phase Ⅱ
timeFrame: 14 day (emergency schedule)/28 days (routine schedule) after the booster dose （only for days 0,14 and days 0,28 schedule）
measure: Immunogenicity indexes of the seroconversion rate, seropositive rate, GMT, and GMI in Phase Ⅰ
timeFrame: 7/14/21 days after the first dose vaccination (emergency schedule)
measure: Immunogenicity indexes of the seroconversion rate, seropositive rate, GMT, and GMI in Phase Ⅰ
timeFrame: 28/35/42 days after the first dose vaccination (routine schedules)
measure: Immunogenicity indexes of the seropositive rate of IgG, IgM antibodies
timeFrame: 7/14/21/28/42 days after the first dose vaccination (emergency schedule)
measure: Immunogenicity indexes of the seropositive rate of IgG,IgM antibodies
timeFrame: 28/35/42/56 days after the first dose vaccination (routine schedule)
Other outcomes:
Locations:
city: Xuzhou
country: China
facility: Suining County Center for Disease Control and Prevention
state: Jiangsu
Study officials:
affiliation: Jiangsu Provincial Center for Disease Control and Prevention
name: Fengcai Zhu, Doctor
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: Zhang Y, Zeng G, Pan H, Li C, Hu Y, Chu K, Han W, Chen Z, Tang R, Yin W, Chen X, Hu Y, Liu X, Jiang C, Li J, Yang M, Song Y, Wang X, Gao Q, Zhu F. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis. 2021 Feb;21(2):181-192. doi: 10.1016/S1473-3099(20)30843-4. Epub 2020 Nov 17.