Study on Combined Vaccination With SARS-CoV-2 Inactivated Vaccine and Quadrivalent Influenza Vaccine

• ClinicalTrials.gov Identifier: NCT04801888
• Recruitment Status: Completed
• First Posted: March 17, 2021
• Last Update Posted: July 26, 2021
• 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 an open-label, single-center, randomized phase IV 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 concomitant administration of the SARS-CoV-2 Inactivated Vaccine (Vero cell) with Quadrivalent Influenza Vaccine in adults aged from 18 to 59 Years

Condition or disease	Intervention/treatment	Phase
COVID-19; Influenza	Biological: Two doses of inactivated SARS-CoV-2 vaccine at the schedule of day 0,28 and one dose Quadrivalent Influenza Vaccine on day 0 or day 28.; Biological: Two doses of inactivated SARS-CoV-2 vaccine at the schedule of day 0,28 and one dose Quadrivalent Influenza Vaccine on day 14.	Phase 4

Detailed Description:

This study is an open-label, single-center, randomized phase IV clinical trial of the SARS-CoV-2 inactivated vaccine (Vero cell) manufactured by Sinovac Research & Development Co., Ltd. The purpose of this study is to evaluate the safety and immunogenicity of concomitant administration of the SARS-CoV-2 Inactivated Vaccine (Vero cell) with Quadrivalent Influenza Vaccine in adults aged from 18 to 59 Years. 480 healthy adults as participants are randomly assigned into two groups in the ratio 1:1. The first group was the combined immunization group, which is randomly divided into two subgroups, 120 subjects in each group. The combined immunization subgroup Ⅰ receive SARS-CoV-2 inactivated vaccine &Quadrivalent Influenza Vaccine on day 0 and SARS-CoV-2 inactivated vaccine (second dose) on day 28.The combined immunization subgroup Ⅱ receive SARS-CoV-2 inactivated vaccine on day 0 and SARS-CoV-2 inactivated vaccine (second dose) & Quadrivalent Influenza Vaccine on day 28. The second group was the non combined immunization group，which receive SARS-CoV-2 inactivated vaccine (first dose) on day 0, Quadrivalent Influenza Vaccine on day 14 and SARS-CoV-2 inactivated vaccine (second dose) on day 28.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 480 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Study to Evaluate the Safety and Immunogenicity of Concomitant Administration of the SARS-CoV-2 Inactivated Vaccine (Vero Cell) With Quadrivalent Influenza Vaccine in Adults Aged From 18 to 59 Years
• Actual Study Start Date: March 23, 2021
• Actual Primary Completion Date: May 28, 2021
• Actual Study Completion Date: May 28, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Combined immunization group; The combined immunization group is randomly divided into two subgroups, 120 subjects in each group. The combined immunization subgroup Ⅰ receive SARS-CoV-2 inactivated vaccine (Vero cell)&Quadrivalent Influenza Vaccine on day0 and SARS-CoV-2 inactivated vaccine (Vero cell) (second dose) on day 28.The combined immunization subgroup Ⅱ receive SARS-CoV-2 inactivated vaccine (Vero cell) on day 0 and SARS-CoV-2 inactivated vaccine (Vero cell) (second dose) & Quadrivalent Influenza Vaccine on day 28.	Biological: Two doses of inactivated SARS-CoV-2 vaccine at the schedule of day 0,28 and one dose Quadrivalent Influenza Vaccine on day 0 or day 28.; The inactivated SARS-CoV-2 vaccine was manufactured by Sinovac Research & Development Co., Ltd., with a antigen content of 600SU/0.5ml. The Quadrivalent Influenza Vaccine manufactured by Sinovac Biotech Co.,Ltd. including 4 antigens H1N1, H3N2, BV and BY, 15μg for each, 0.5ml per dose.
Experimental: Non combined immunization group; The non combined immunization group receive SARS-CoV-2 inactivated vaccine (Vero cell)(first dose) on day 0, Quadrivalent Influenza Vaccine on day 14 and SARS-CoV-2 inactivated vaccine (Vero cell)(second dose) on day 28.	Biological: Two doses of inactivated SARS-CoV-2 vaccine at the schedule of day 0,28 and one dose Quadrivalent Influenza Vaccine on day 14.; The inactivated SARS-CoV-2 vaccine was manufactured by Sinovac Research & Development Co., Ltd., with a antigen content of 600SU/0.5ml. The Quadrivalent Influenza Vaccine manufactured by Sinovac Biotech Co.,Ltd. including 4 antigens H1N1, H3N2, BV and BY, 15μg for each, 0.5ml per dose.

Outcome Measures

Primary Outcome Measures :

1. Safety index-incidence of adverse reactions within 7 days after each dose [ Time Frame: Day 0-7 after each dose vaccination ]
   Incidence of adverse reactions within 7 days after each dose
2. Immunogenicity index-seroconversion rates of neutralizing antibody against SARS-CoV-2 [ Time Frame: The 28th day after the second dose vaccination of the inactivated SARS-CoV-2 vaccine ]
   Neutralizing antibody assay will be performed using the micro-neutralization method. Seroconversion will be defined as a change from seronegative (<1:8) to seropositive (≥1:8), or ≥4 fold increase from baseline.

Secondary Outcome Measures :

1. Safety index-incidence of adverse reactions within 56 days after the first dose vaccination [ Time Frame: Day 0-56 after the first dose vaccination ]
   Incidence of adverse reactions within 56 days after the first dose vaccination
2. Safety index-incidence of serious adverse events [ Time Frame: Day 0-56 after the first dose vaccination ]
   SAE will be collected throughout the clinical trial.
3. Immunogenicity index-seropositive rates of neutralizing antibody against SARS-CoV-2 [ Time Frame: The 28th day after each dose vaccination ]
   Neutralizing antibody assay will be performed using the micro-neutralization method, and subjects with a antibody titer ≥1:8 will defined as seropositive.
4. Immunogenicity index-geometric mean titer (GMT) of neutralizing antibody against SARS-CoV-2 [ Time Frame: The 28th day after each dose vaccination ]
   Neutralizing antibody assay will be performed using the micro-neutralization method.
5. Immunogenicity index-geometric mean ratio (GMR) of neutralizing antibody against SARS-CoV-2 [ Time Frame: The 28th day after each dose vaccination ]
   Neutralizing antibody assay will be performed using the micro-neutralization method. Ratio of post-vaccination titer divided by baseline titer will be calculated.
6. Immunogenicity index-seroconversion rates of influenza HI antibodies [ Time Frame: The 28th day after the vaccination ]
   Seroconversion will be defined as a change from seronegative (<1:10) to protective (≥1:40), or ≥4 fold increase from baseline(≥1:10).
7. Immunogenicity index-protective rates of influenza HI antibodies [ Time Frame: The 28th day after the vaccination ]
   The standard of reaching the protective rate is that the antibody titer ≥1:40.
8. Immunogenicity index-geometric mean titer (GMT) of influenza HI antibodies [ Time Frame: The 28th day after the vaccination ]
   influenza HI antibodies assay will be performed using the micro hemagglutination inhibition test
9. Immunogenicity index-geometric mean ratio (GMR) of influenza HI antibodies [ Time Frame: The 28th day after the vaccination ]
   influenza HI antibodies assay will be performed using the micro hemagglutination inhibition test

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;
• The subject can understand and voluntarily sign the informed consent form;
• Proven legal identity

Exclusion Criteria:

• Travel history / residence history of 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 communities with case reports within 14 days;
• Two or more cases of fever and / or respiratory symptoms in a small contact area of volunteers, such as home, office etc. within 14 days;
• History of SARS-CoV-2 infection;
• 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;
• Severe chronic diseases, severe cardiovascular diseases, hypertension and diabetes that cannot be controlled by drugs, liver or 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 noncomplicated dermatitis superficial corticosteroid therapy) in the past 6 months;

• Physical examination has clinically significant abnormal hematology and biochemistry laboratory test results that exceed the reference value range (only applicable to phase I clinical trials):

  1. Blood routine test: white blood cell count, hemoglobin, platelet count;
  2. Detection of blood biochemical indicators: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), creatinine (CR), fasting blood glucose;
  3. Urine routine index: urine protein (PRO);
• 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;
• Acute diseases or acute exacerbation of chronic diseases in the past 7 days;
• Axillary temperature >37.0°C;
• Already pregnant (including a positive urine pregnancy test) or are breastfeeding, planning to get pregnant within 3 months;
• 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, Zhejiang

Kaihua county Center for Disease Control and Prevention

Quzhou, Zhejiang, China, 324300

Sponsors and Collaborators

Sinovac Research and Development Co., Ltd.

Investigators

• Principal Investigator: Huakun Lv, Master; Zhejiang Provincial Center for Disease Control and Prevention

More Information

• Responsible Party: Sinovac Research and Development Co., Ltd.
• ClinicalTrials.gov Identifier: NCT04801888
• Other Study ID Numbers: PRO-QINF-4001
• First Posted: March 17, 2021
• Last Update Posted: July 26, 2021
• Last Verified: March 2021

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

Additional relevant MeSH terms:

Influenza, Human; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs