Evaluation of Immunogenicity and Safety of Combined Immunization of COVAX (Produced in Wuhan) and PPV23 / IIV4

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 Wuhan) and 23-valent Pneumococcal Polysaccharide Vaccine (PPV23) or Quadrivalent Inactivated Influenza Vaccine (IIV4)

Subjects will be recruited and divided into 3 groups:

Experimental Group (468 subjects): 1st dose : combined vaccination of COVAX+PPV23, 2nd dose: combined vaccination of COVAX+IIV4; Control Group A (468 subjects): 1st dose: COVAX only, 2nd dose: COVAX only; Control Group B (468 subjects): 1st dose: PPV23 only, 2nd dose: IIV4 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pneumonia, Pneumococcal; Influenza, Human; COVID-19 Pneumonia
• Intervention / Treatment: Biological: COVAX+PPV23;COVAX+IIV4; Biological: COVAX only (1st and 2nd dose); Biological: PPV23 for the 1st dose and IIV4 for the 2nd dose

Detailed Description

This randomized, parallel, controlled study is designed to evaluate the immunogenicity and safety of simultaneously immunization of COVAX + PPV23 and COVAX + IIV4.

1404 subjects are divided into 3 groups, including 1 experimental group and 2 control groups (control group A and B). Each group includes 468 subjects respectively.

Experimental Group (468 subjects) will receive: 1st dose : combined vaccination of COVAX+PPV23, 2nd dose: combined vaccination of COVAX+IIV4; Control Group A (468 subjects) will receive: 1st dose: COVAX only, 2nd dose: COVAX only; Control Group B (468 subjects) will receive: 1st dose: PPV23 only, 2nd dose: IIV4 only.

Specifically, each group will be divided again. Each 468-subject group is divided again into 2 age-based subgroups: (1) 18-59 years old; (2) ≥60 years old.

Each subgroup includes 234 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.

• Study Type: Interventional
• Enrollment (Actual): 1404
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Guangdong Center for Disease Control and Prevention
  • Henan
    • Zhengzhou, Henan, China
      • Henan Center for Disease Control and Prevention
  • Hubei
    • Wuhan, Hubei, China
      • Hubei Center for Disease Control and Prevention

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Experimental Group (468 subjects) will receive: 1st dose : combined vaccination of COVAX+PPV23; 2nd dose: combined vaccination of COVAX+IIV4	Biological: COVAX+PPV23;COVAX+IIV4; 1st dose : combined vaccination of COVAX+PPV23; 2nd dose: combined vaccination of COVAX+IIV4
Active Comparator: Control group A; Control Group A (468 subjects) will receive: 1st dose: COVAX only; 2nd dose: COVAX only	Biological: COVAX only (1st and 2nd dose); 1st dose: COVAX only; 2nd dose: COVAX only
Active Comparator: Control group B; Control Group B (468 subjects) will receive: 1st dose: PPV23 only; 2nd dose: IIV4 only	Biological: PPV23 for the 1st dose and IIV4 for the 2nd dose; 1st dose: PPV23 only; 2nd dose: IIV4 only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroconversion rate (COVAX)	the rate of positive seroconversion against coronavirus	Results obtained 28 days after the first dose (= right before the second dose)
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)
Neutralizing antibody level (COVAX)	neutralizing antibody level against coronavirus	Baseline (before vaccination) results
Neutralizing antibody level (COVAX)	neutralizing antibody level against coronavirus	Results obtained 28 days after the first dose (= right before the second dose)
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)
Seropositive rate (IIV4)	the rate of positive seroconversion against influenza A (H3N2, H1N1) type and B (BY, BV) type viruses	Baseline (before vaccination) results
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)
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)
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
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)
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)
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)
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)
Neutralizing antibody level (PPV23)	Neutralizing antibody level against 23 pneumococcal serotypes	Baseline (before vaccination) results
Neutralizing antibody level (PPV23)	Neutralizing antibody level against 23 pneumococcal serotypes	Results obtained 28 days after the first dose (= right before the second dose)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events following vaccination	analyse the incidence of adverse events following immunization, both solicited and unsolicited	0-6 months

Collaborators and Investigators

• Sponsor: China National Biotec Group Company Limited
• Collaborators: Wuhan Institute of Biological Products Co., Ltd; Henan Center for Disease Control and Prevention; Hubei Provincial Center for Disease Control and Prevention; Chengdu Institute of Biological Products Co.,Ltd.; Changchun Institute of Biological Products Co., Ltd.; Guangdong Center for Disease Prevention and Control

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2021
• Primary Completion (Actual): May 29, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: October 5, 2021
• First Submitted That Met QC Criteria: October 5, 2021
• First Posted (Actual): October 15, 2021

Study Record Updates

• Last Update Posted (Actual): October 15, 2021
• Last Update Submitted That Met QC Criteria: October 5, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumonia, Bacterial; Orthomyxoviridae Infections; Pneumococcal Infections; Pneumonia; Pneumonia, Pneumococcal; Influenza, Human
• Other Study ID Numbers: COVAX+PPV23+IIV4-Wuhan

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No