Evaluation of Immunogenicity and Safety of Combined Immunization of COVID-19 Vaccine (Produced in Beijing) and PPV23 / IIV4

Covid19 Clinical Trial

Official title:

A Randomized, Controlled, Multicenter Phase 4 Clinic Trial to Evaluate the Immunogenicity and Safety of Combined Immunization of Inactivated SARS-CoV-2 Vaccines (Vero Cell) (COVAX) (Produced in Beijing) and 23-valent Pneumococcal Polysaccharide Vaccine (PPV23) or Quadrivalent Inactivated Influenza Vaccine (IIV4)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04790851
• Other study ID #: COVAX+PPV23+IIV4-Beijing
• Status: Completed
• Phase: Phase 4
• Start date: March 10, 2021
• Est. completion date: September 5, 2021

Study information

• Verified date: October 2021
• Source: China National Biotec Group Company Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Subjects will be recruited and divided into 3 groups: Experimental Group (384 subjects): 1st dose : combined vaccination of COVAX+IIV4, 2nd dose: combined vaccination of COVAX+PPV23; Control Group A (384 subjects): 1st dose: COVAX only, 2nd dose: COVAX only; Control Group B (384 subjects): 1st dose: IIV4 only, 2nd dose: PPV23 only. Blood samples will be collected 3 times: before the 1st dose of vaccinatioin; before the 2nd dose of vaccination; 28 days after the 2nd dose of vaccination. The immunogenicity and safety of both experimental and control groups will be analyzed.

Description:

This randomized, parallel, controlled study is designed to evaluate the immunogenicity and safety of simultaneously immunization of COVAX + PPV23 and COVAX + IIV4. 1152 subjects are divided into 3 groups, including 1 experimental group and 2 control groups (control group A and B). Each group includes 384 subjects respectively. Experimental Group (384 subjects) will receive: 1st dose : combined vaccination of COVAX+IIV4, 2nd dose: combined vaccination of COVAX+PPV23; Control Group A (384 subjects) will receive: 1st dose: COVAX only, 2nd dose: COVAX only; Control Group B (384 subjects) will receive: 1st dose: IIV4 only, 2nd dose: PPV23 only. Specifically, each group will be divided again. Each 384-subject group is divided again into 2 age-based subgroups: (1) 18-59 years old; (2) ≥60 years old. Each subgroup includes 192 subjects respectively. Blood samples will be collected 3 times: (1) before the 1st dose of vaccinatioin; (2) before the 2nd dose of vaccination; (3) 28 days after the 2nd dose of vaccination. To evaluate the immunogenicity, the investigators will detect and compare the neutralizing antibody levels, the seroconversion rates and antibody geometric mean concentrations. The safety of all groups will be monitored as well.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1133
• Est. completion date: September 5, 2021
• Est. primary completion date: September 5, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• =18 years old when enrolled;
• Participants signing the informed consent;
• Being able to participate in all planned follow-ups and accomplish all research procedures including completing a diary card and coming back for interview;
• Having not been administered any pneumonia vaccine or COVID-19 vaccine, and having not been administered an influenza vaccine in the current season before enrollment;
• =14 days from the most recent vaccination;
• Before enrollment, the body temperature is =37.0C as confirmed by medical history and clinical examination.

Exclusion criteria for the first dose:

• Having a history of COVID-19 or a positive nucleic acid test for COVID-19;
• Having a history or a family history of allergy, convulsion, epilepsy, brain disease, or mental illness;
• Being allergic to any component of vaccines, or having a history of severe allergic reaction to any vaccine;
• Having immunodeficiency disorder, during treatment of malignant tumor, having immunodeficiency induced by immunosuppressants (oral steroid hormones) or HIV, or having a family member with close contact who suffers from congenital immune disorder;
• Having injection of non-specific immunoglobulin within 1 month prior to enrollment;
• Having acute febrile illness or communicable disease;
• Having a history of confirmed thrombocytopenia or other coagulation disorders, which may cause contraindications for a subcutaneous injection;
• Having severe chronic disease or acute exacerbation of chronic disease, or having uncontrolled hypertension or diabetes;
• Having various infectious, pyogenic, or allergic skin diseases;
• Women in pregnancy or lactation or participants who plan for a baby within 3 months after vaccination should delay the vaccination;
• Having any condition that may affect trial assessment as determined by researchers.

Exclusion criteria for the second dose:

• Having any serious adverse event related to the first dose vaccination;
• After vaccination, having systemic adverse reaction or allergic reaction with a severity of grade 3 or higher as determined by researchers;
• Having a newly emerging condition that meets the exclusion criteria for the first dose;
• Having any condition that may affect trial assessment as determined by researchers.

Related Conditions & MeSH terms

• COVID-19
• Covid19
• Influenza, Human
• Pneumonia, Pneumococcal

Intervention

Biological:
• COVAX+IIV4; COVAX+PPV23
1st dose : combined vaccination of COVAX+IIV4; 2nd dose: combined vaccination of COVAX+PPV23
• COVAX only (1st and 2nd dose)
1st dose: COVAX only; 2nd dose: COVAX only
• IIV4 for the 1st dose and PPV23 for the 2nd dose
1st dose: IIV4 only; 2nd dose: PPV23 only

Locations

Country	Name	City	State
China	Sichuan Center for Disease Control and Prevention	Chengdu
China	Shanghai Municipal Center for Disease Control and Prevention	Shanghai
China	Shanxi Provincial Center for Disease Control and Prevention	Taiyuan

Sponsors (7)

Lead Sponsor	Collaborator
China National Biotec Group Company Limited	Beijing Institute of Biological Products Co Ltd., Changchun Institute of Biological Products Co., Ltd., Chengdu Institute of Biological Products Co.,Ltd., Shanghai Municipal Center for Disease Control and Prevention, Shanxi Center for Disease Control and Prevention, Sichuan Center for Disease Control and Prevention

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Seroconversion rate (COVAX)	the rate of positive seroconversion against coronavirus	Results obtained 28 days after the first dose (= right before the second dose)
Primary	Seroconversion rate (COVAX)	the rate of positive seroconversion against coronavirus	Results obtained after the second dose of vaccination (= 56 days after the first dose, or 28 days after the second dose)
Primary	Neutralizing antibody level (COVAX)	neutralizing antibody level against coronavirus	Baseline (before vaccination) results
Primary	Neutralizing antibody level (COVAX)	neutralizing antibody level against coronavirus	Results obtained 28 days after the first dose (= right before the second dose)
Primary	Neutralizing antibody level (COVAX)	neutralizing antibody level against coronavirus	Results obtained after the second dose of vaccination (= 56 days after the first dose, or 28 days after the second dose)
Primary	Seropositive rate (IIV4)	the rate of positive seroconversion against influenza A (H3N2, H1N1) type and B (BY, BV) type viruses	Baseline (before vaccination) results
Primary	Seroconversion rate (IIV4)	the rate of positive seroconversion against influenza A (H3N2, H1N1) type and B (BY, BV) type viruses	Results obtained 28 days after the first dose (= right before the second dose)
Primary	Seroconversion rate (IIV4)	the rate of positive seroconversion against influenza A (H3N2, H1N1) type and B (BY, BV) type viruses	Results obtained after the second dose of vaccination (= 56 days after the first dose, or 28 days after the second dose)
Primary	Hemmagglution inhibition antibody level (IIV4)	Hemmagglution inhibition antibody levels against influenza A (H3N2, H1N1) type and B (BY, BV) type viruses	Baseline (before vaccination) results
Primary	Hemmagglution inhibition antibody level (IIV4)	Hemmagglution inhibition antibody levels against influenza A (H3N2, H1N1) type and B (BY, BV) type viruses	Results obtained 28 days after the first dose (= right before the second dose)
Primary	Hemmagglution inhibition antibody level (IIV4)	Hemmagglution inhibition antibody levels against influenza A (H3N2, H1N1) type and B (BY, BV) type viruses	Results obtained after the second dose of vaccination (= 56 days after the first dose, or 28 days after the second dose)
Primary	Seroconversion rate (PPV23)	the rate of positive seroconversion against 23 pneumococcal serotypes	Results obtained 28 days after the first dose (= right before the second dose)
Primary	Seroconversion rate (PPV23)	the rate of positive seroconversion against 23 pneumococcal serotypes	Results obtained after the second dose of vaccination (= 56 days after the first dose, or 28 days after the second dose)
Primary	Neutralizing antibody level (PPV23)	Neutralizing antibody level against 23 pneumococcal serotypes	Baseline (before vaccination) results
Primary	Neutralizing antibody level (PPV23)	Neutralizing antibody level against 23 pneumococcal serotypes	Results obtained 28 days after the first dose (= right before the second dose)
Primary	Neutralizing antibody level (PPV23)	Neutralizing antibody level against 23 pneumococcal serotypes	Results obtained after the second dose of vaccination (= 56 days after the first dose, or 28 days after the second dose)
Secondary	Adverse events following vaccination	analyse the incidence of adverse events following immunization, both solicited and unsolicited	0-6 months