Safety and Immunogenicity Study of Inactivated Vaccine for Prophylaxis of SARS CoV-2 Infection (COVID-19)

• ClinicalTrials.gov Identifier: NCT04352608
• Recruitment Status: Completed
• First Posted: April 20, 2020
• Last Update Posted: February 24, 2022
• Sponsor: Sinovac Research and Development Co., Ltd.
• Information provided by (Responsible Party): Sinovac Biotech Co., Ltd ( Sinovac Research and Development Co., Ltd. )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
COVID-19	Biological: Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule; Biological: Two doses of high dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule; Biological: Two doses of placebo at the emergency vaccination schedule; Biological: Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule; Biological: Two doses of high dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule; Biological: Two doses of placebo at the routine vaccination schedule; Biological: Three doses of medium dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule; Biological: Three doses of high dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule; Biological: Three doses of placebo at the emergency vaccination schedule; Biological: Three doses of medium dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule; Biological: Three doses of high dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule; Biological: Three doses of placebo at the routine vaccination schedule	Phase 1; Phase 2

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 .

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 744 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• 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
• Actual Study Start Date: April 16, 2020
• Actual Primary Completion Date: July 10, 2020
• Actual Study Completion Date: July 24, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Emergency schedule & Two doses of medium dosage vaccine; 24 participants in phase Ⅰand 60 participants in phase Ⅱ will receive two doses of medium dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule,and 60 participants in phase Ⅱ will receive one dose of booster immunization with medium dosage vaccine 6 months after the emergency schedule	Biological: Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule; Two doses of medium dosage (600SU/0.5ml) experimental vaccine at the schedule of day 0,14,and one dose of booster immunization with medium dosage (600SU/0.5ml) experimental vaccine 6 months after the schedule of day 0,14 in phaseⅡ.
Experimental: Emergency schedule & Two doses of high dosage vaccine; 24 participants in phase Ⅰand 60 participants in phase Ⅱ will receive two doses of high dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule,and 60 participants in phase Ⅱ will receive one dose of booster immunization with high dosage vaccine 6 months after the emergency schedule	Biological: Two doses of high dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule; Two doses of high dosage (1200 SU/0.5ml) experimental vaccine at the schedule of day 0,14 and one dose of booster immunization with high dosage (1200SU/0.5ml) experimental vaccine 6 months after the schedule of day 0,14 in phaseⅡ.
Placebo Comparator: Emergency schedule &Two doses of placebo; 24 participants in phase Ⅰand 30 participants in phase Ⅱ will receive two doses of placebo at the emergency vaccination schedule,and 30 participants in phase Ⅱ will receive one dose of booster immunization with placebo 6 months after the emergency schedule	Biological: Two doses of placebo at the emergency vaccination schedule; Two doses of placebo at the schedule of day 0,14 and one dose of booster immunization with placebo 6 months after the schedule of day 0,14 in phaseⅡ.
Experimental: Routine schedule & Two doses of medium dosage vaccine; 24 participants in phase Ⅰand 60 participants in phase Ⅱ will receive two doses of medium dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule,and 60 participants in phase Ⅱ will receive one dose of booster immunization with medium dosage vaccine 6 months after the routine schedule	Biological: Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule; Two doses of medium dosage (600SU/0.5ml) experimental vaccine at the schedule of day 0,28 and one dose of booster immunization with medium dosage (600SU/0.5ml) experimental vaccine 6 months after the schedule of day 0,28 in phaseⅡ.
Experimental: Routine schedule &Two doses of high dosage vaccine; 24 participants in phase Ⅰand 60 participants in phase Ⅱ will receive two doses of high dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule,and 60 participants in phase Ⅱ will receive one dose of booster immunization with high dosage vaccine 6 months after the routine schedule	Biological: Two doses of high dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule; Two doses of high dosage (1200 SU/0.5ml) experimental vaccine at the schedule of day 0,28 and one dose of booster immunization with high dosage (1200SU/0.5ml) experimental vaccine 6 months after the schedule of day 0,28 in phaseⅡ
Placebo Comparator: Routine schedule & Two doses of placebo; 24 participants in phase Ⅰand 30 participants in phase Ⅱ will receive two doses of placebo at the routine vaccination schedule,and 30 participants in phase Ⅱ will receive one dose of booster immunization with placebo 6 months after the routine schedule	Biological: Two doses of placebo at the routine vaccination schedule; Two doses of placebo at the schedule of day 0,28 and one dose of booster immunization with placebo 6 months after the schedule of day 0,28 in phaseⅡ.
Experimental: Emergency schedule & Three doses of medium dosage vaccine; 60 participants in phase Ⅱ will receive three doses of medium dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule	Biological: Three doses of medium dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule; Three doses of medium dosage (600SU/0.5ml) experimental vaccine at the schedule of day 0,14,42
Experimental: Emergency schedule & Three doses of high dosage vaccine; 60 participants in phase Ⅱ will receive three doses of high dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule	Biological: Three doses of high dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule; Three doses of high dosage (1200 SU/0.5ml) experimental vaccine at the schedule of day 0,14,42
Placebo Comparator: Emergency schedule &Three doses of placebo; 30 participants in phase Ⅱ will receive three doses of placebo at the emergency vaccination schedule	Biological: Three doses of placebo at the emergency vaccination schedule; Three doses of placebo at the schedule of day 0,14,42
Experimental: Routine schedule & Three doses of medium dosage vaccine; 60 participants in phase Ⅱ will receive three doses of medium dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule	Biological: Three doses of medium dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule; Three doses of medium dosage (600SU/0.5ml) experimental vaccine at the schedule of day 0,28,56
Experimental: Routine schedule &Three doses of high dosage vaccine; 60 participants in phase Ⅱ will receive three doses of high dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule	Biological: Three doses of high dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule; Three doses of high dosage (1200 SU/0.5ml) experimental vaccine at the schedule of day 0,28,56
Placebo Comparator: Routine schedule &Three doses of placebo; 30 participants in phase Ⅱ will receive three doses of placebo at the routine vaccination schedule	Biological: Three doses of placebo at the routine vaccination schedule; Three doses of placebo at the schedule of day 0,28,56

Outcome Measures

Primary Outcome Measures :

1. Safety indexes of adverse reactions [ Time Frame: From Day 0 to Day 28 after each dose ]
   Incidence of adverse reactions occured from Day 0 to Day 28 after each dose
2. Immunogenicity indexes of neutralizing-antibody seroconversion rates [ Time Frame: The 14th day /the 28th day after two doses of vaccination ]
   The seroconversion rate of neutralizing antibodies 14 days (emergency schedule)/28 days (routine schedule) after the two-dose vaccination.

Secondary Outcome Measures :

1. Safety indexes of adverse reactions [ Time Frame: 7 days after each dose of vaccination ]
   Incidence of adverse reactions 7 days after each dose of vaccination
2. Safety indexes of Incidence of abnormal laboratory index [ Time Frame: On the 3th day after each dose of vaccination in phase Ⅰ ]
   Incidence of abnormal laboratory index (blood routine test, blood chemistry test,and urine routine test) on the 3th day after each dose of vaccination in phase Ⅰ
3. Safety indexes of serious adverse events (SAEs） [ Time Frame: From the beginning of the vaccination to 6 months post the whole-schedule vaccination ]
   Incidence of SAEs from the beginning of the vaccination to 6 months post the whole-schedule vaccination
4. Immunogenicity indexes of the seropositive rate, GMT, and GMI of neutralizing antibodies [ Time Frame: 14 days (emergency schedule)/28 days (routine schedule) after two-dose vaccination ]
   The seropositive rate, GMT, and GMI of neutralizing antibodies 14 days (emergency schedule)/28 days (routine schedule) after two-dose vaccination
5. Immunogenicity indexes of the seroconversion rate, seropositive rate, GMT and GMI of neutralizing antibodies [ Time Frame: 28 days after the two doses (emergency schedule) ]
   The seroconversion rate, seropositive rate, GMT and GMI of neutralizing antibodies 28 days after the two doses (emergency schedule)
6. Immunogenicity indexes of the seroconversion rate, seropositive rate, GMT, and GMI in Phase Ⅱ [ Time Frame: 28 days after the third dose （only for days 0,14,42 and days 0,28,56 schedule） ]
   Phase Ⅱ:The seroconversion rate, seropositive rate, GMT, and GMI 28 days after the third dose（only for days 0,14,42 and days 0,28,56 schedule）
7. Immunogenicity indexes of the seropositivity rate, GMT, and GMI in Phase Ⅱ [ Time Frame: 14 day (emergency schedule)/28 days (routine schedule) after the booster dose （only for days 0,14 and days 0,28 schedule） ]
   Phase Ⅱ:The seropositivity rate, GMT, and GMI 14 day (emergency schedule)/28 days (routine schedule) after the booster dose （only for days 0,14 and days 0,28 schedule）
8. Immunogenicity indexes of the seroconversion rate, seropositive rate, GMT, and GMI in Phase Ⅰ [ Time Frame: 7/14/21 days after the first dose vaccination (emergency schedule) ]
   Phase Ⅰ:The seroconversion rate, seropositive rate, GMT, and GMI 7/14/21 days after the first dose vaccination (emergency schedule)
9. Immunogenicity indexes of the seroconversion rate, seropositive rate, GMT, and GMI in Phase Ⅰ [ Time Frame: 28/35/42 days after the first dose vaccination (routine schedules) ]
   Phase Ⅰ:The seroconversion rate, seropositive rate, GMT, and GMI 28/35/42 days after the first dose vaccination (routine schedules)
10. Immunogenicity indexes of the seropositive rate of IgG, IgM antibodies [ Time Frame: 7/14/21/28/42 days after the first dose vaccination (emergency schedule) ]
    Phase Ⅰ:The seropositive rate of IgG, IgM antibodies 7/14/21/28/42 days after the first dose vaccination (emergency schedule)
11. Immunogenicity indexes of the seropositive rate of IgG,IgM antibodies [ Time Frame: 28/35/42/56 days after the first dose vaccination (routine schedule) ]
    Phase Ⅰ: The seropositive rate of IgG,IgM antibodies 28/35/42/56 days after the first dose vaccination (routine schedule)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 59 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

China, Jiangsu

Suining County Center for Disease Control and Prevention

Xuzhou, Jiangsu, China, 221200

Sponsors and Collaborators

Sinovac Research and Development Co., Ltd.

Investigators

• Principal Investigator: Fengcai Zhu, Doctor; Jiangsu Provincial Center for Disease Control and Prevention

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

• Responsible Party: Sinovac Research and Development Co., Ltd.
• ClinicalTrials.gov Identifier: NCT04352608
• Other Study ID Numbers: PRO-nCOV-1001
• First Posted: April 20, 2020
• Last Update Posted: February 24, 2022
• Last Verified: July 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs