Evaluation of the Safety and Immunogenicity of Simultaneously Administration of EV71 Vaccine and Influenza Vaccine

A Randomized, Controlled, Multicenter Phase 4 Clinic Trial to Evaluate the Safety and Immunogenicity of Simultaneously Administration of EV71 Vaccine and Influenza Vaccine (Split Virion),Inactivated

Subjects will be recruited and divided into 3 groups:

1. Experimental Group (378 subjects): combined immunization of EV71 vaccine and influenza vaccine;
2. Control Group A (378 subjects): EV71 vaccine only;
3. Control Group B (378 subjects): influenza vaccine only;

All blood samples will be collected before and one month after vaccinatioin. The immunogenicity and safety of both experimental and control groups will be compared and the data be analyzed.

Study Overview

• Status: Completed
• Conditions: Enterovirus Infections; Influenza
• Intervention / Treatment: Biological: EV71 vaccine and influenza vaccine; Biological: EV71 vaccine; Biological: influenza vaccine

Detailed Description

To further evaluate the feasibility of simultaneously administration of EV71 vaccine and flu vaccine, we design this clinical trial to test its immunogenicity and safety. 1134 subjects aged from 6 to 11 months old are divided into one experimental group and two control groups (control group A and B).

378 subjects from the experimental group will be simultaneously administrated with one dose of EV71 vaccine (0.5 ml) and one dose of influenza vaccine (0.25 ml). One month later, they are going to receive a second dose of EV71 vaccine and influenza vaccine, simultaneously. Blood samples are collected before the first vaccination, and one month following the second vaccination.

378 subjects from the control group A will be only administrated with two doses of EV71 vaccine (0.5 ml) (1 month apart). Blood samples are collected before the first vaccination, and one month following the second vaccination.

378 subjects from the control group B will be only administrated with two doses of influenza vaccine (0.25 ml) (1 month apart). Blood samples are collected before the first vaccination, and one month following the second vaccination.

To evaluate the immunogenicity, we will detect and compare the neutralization antibody levels, the seroprotection rates, and antibody geometric mean concentrations. The safety of all groups will be monitored as well.

• Study Type: Interventional
• Enrollment (Actual): 1134
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310051
      • Zhejiang Provincial Center for Disease Control and Prevention

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 11 months (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• subjects aged from 6-11 months old at the date of recruitment;
• with informed consent signed by parent(s) or guardians;
• parent(s) or guardians are able to attend all planned clinical appointments and comply with all study instructions;
• subjects not receive any vaccination within 14 days at the date of recruitment;
• subjects have not been vaccinated with EV71 vaccine, seasonal flu vaccine;
• subjects with no medical history of EV71 infection;
• axillary temperature ≤37.0℃

Exclusion Criteria:

• subject who has a medical history with Hypersensitiveness, eclampsia, epilepsy, cerebropathia and neurological illness;
• allergic to any ingredient of vaccine or with allergy history to any vaccine;
• subjects with immunodeficency or suspected impairment of immunologic function (e.g. caused by HIV), or subjects are in the process of immunosuppressor therapy(Taking orally injecting of steroid hormone);
• administration of immunoglobulins within 30 days prior to this study;
• acute febrile disease(temperature ≥ 37.0°C) or infectious disease;
• have a clearly diagnosed history of thrombocytopenia or other coagulopathy,
• may cause contraindications for subcutaneous injection;
• any serious chronic illness, acute infectious diseases, or respiratory diseases;
• severe cardiovascular disease, liver and kidney diseases or diabetes mellitus with complications;
• any kind of infectious, purulent, or allergic skin diseases;
• any other factor that makes the investigator determines the subject is unsuitable for this study.

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; 378 subjects from the experimental group will be simultaneously administrated with one dose of EV71 vaccine (0.5 ml) and one dose of influenza vaccine (0.25 ml). One month later, they are going to receive a second dose of EV71 vaccine and influenza vaccine, simultaneously.	Biological: EV71 vaccine and influenza vaccine; simultaneously administrated with EV71 vaccine and influenza vaccine
Active Comparator: control group A; 378 subjects from the control group A will be only administrated with two doses of EV71 vaccine (0.5 ml) (1 month apart).	Biological: EV71 vaccine; administrated with EV71 vaccine only
Active Comparator: control group B; 378 subjects from the control group B will be only administrated with two doses of influenza vaccine (0.25 ml) (1 month apart).	Biological: influenza vaccine; administrated with influenza vaccine only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroconversion rate I	the rate of positive seroconversion against EV71	Baseline (before vaccination) and 1 month after the last dose
Seroconversion rate II	the rate of positive seroconversion against Influenza A (H3N2, H1N1) and B Type viruses	Baseline (before vaccination ) and 1 month after the last dose
Geometric mean titer (GMT) I	Measure neutralizing antibody titers against EV71	Baseline (before vaccination) and 1 month after the last dose
Geometric mean titer (GMT) II	Measure neutralizing antibody titers against Influenza A (H3N2, H1N1) and B Type viruses	Baseline (before vaccination) and 1 month after the last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse events following vaccination	analyse the numbers and rates of participants who experience adverse events following immunization	6 months

Collaborators and Investigators

• Sponsor: China National Biotec Group Company Limited
• Collaborators: Peking University; Wuhan Institute of Biological Products Co., Ltd; Guizhou Center for Disease Control and Prevention; National Institutes for Food and Drug Control, China; Henan Center for Disease Control and Prevention; Zhejiang Provincial Center for Disease Control and Prevention; Changchun Institute of Biological Products Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2019
• Primary Completion (Actual): January 6, 2020
• Study Completion (Actual): August 10, 2021

Study Registration Dates

• First Submitted: September 15, 2019
• First Submitted That Met QC Criteria: September 16, 2019
• First Posted (Actual): September 17, 2019

Study Record Updates

• Last Update Posted (Actual): October 12, 2022
• Last Update Submitted That Met QC Criteria: October 10, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: influenza vaccine; EV71 vaccine; simultaneously administration
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Picornaviridae Infections; Orthomyxoviridae Infections; Influenza, Human; Enterovirus Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: EV71-Flu-Combine-01

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