Phase IV Clinical Trial, Immunogenicity and Safety of EV71 Vaccine

A Phase IV Open-labelled, Single-centered, Stratified-randomized Clinical Trial in Zhejiang Province to Evaluate the Safety and Immunogenicity of EV71 Vaccine Developed by Sinovac Biotech Co., Ltd.

The purpose of this study is to evaluate the immunogenicity and safety of EV71 vaccine in infants aged 6 to 35 months old, by detecting the dynamic changes of neutralizing antibody at different time after vaccination

Study Overview

• Status: Completed
• Conditions: Hand, Foot and Mouth Disease
• Intervention / Treatment: Biological: EV71 vaccine

Detailed Description

This study is an open-labelled, single-centered, stratified-randomized, phase IV clinical trial. The purpose of this study is to evaluate the immunogenicity and safety of EV71 vaccine (developed by Sinovac Biotech Co., Ltd.) in infants aged 6 to 35 months old, by detecting the dynamic changes of neutralizing antibody at different times after vaccination. The enrolled subjects in this study receive two doses of EV71 vaccine with 1-month interval between doses. To evaluate safety of the vaccine, subjects will be observed for 30 days after the injection for the potential adverse events. To evaluate the immunogenicity of the vaccine, venous blood will be collected for the neutralizing antibody detection prior to vaccination, 10/20/30 days after the 1st dose and 30 days after the 2nd dose vaccination. All subjects will receive blood sampling for three times. Subjects will be randomly assigned to receive blood sampling at 10/20/30 days after 1st dose injection, with a ratio of 1: 1: 1.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Shaoxing, Zhejiang, China, 312300
      • Shangyu District Center for Disease Control and Prevention

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 2 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers aged 6-35 months old
• Guardian(s) of the volunteer should be capable of understanding the written consent form, and such form should be signed before the infant being included into this study
• Proven legal identity

Exclusion Criteria:

For subjects with any of the following conditions, vaccination should not be administrated:

• History of hand foot and mouth disease
• Allergy to gentamicin; history of allergy to any vaccine or vaccine ingredient, or serious adverse reaction(s) to vaccination, such as urticaria, difficulty in breathing, angioneurotic edema, pain, etc
• Severe chronic diseases
• Thrombocytopenia or hemorrhagic disease
• Immunodeficiency disease or receipt of immunosuppressant treatment
• Uncontrolled epilepsy or progressive neurological disorders(e.g. Guillain-Barre syndrome)
• Acute disease or acute stage of chronic disease prior to the study entry
• History of thyroidectomy, thyroid disease within 12 months prior to the study entry
• Asplenia or functional asplenia
• Axillary temperature >37.0 ℃
• Any other factor that suggesting the volunteer is unsuitable for this study based on the judgment of investigators

Exclusion Criteria of the Second Injection:

• Subjects with any of the following conditions are forbidden to continue the 2nd dose of vaccination:

  1. Any serious adverse event that has a causal relationship with the investigated vaccine
  2. Severe allergic reactions or hypersensitivity after vaccination (including urticaria / rash appear within 30 minutes after vaccination
  3. Any confirmed or suspected autoimmune disease or immunodeficiency disease (e.g., HIV infection)
  4. Other reactions (including severe pain, severe swelling, severe activity limitation, persistent hyperthermia, severe headache or other systemic or local reactions)determined by the investigators
• For subjects suffering from acute disease or acute stage of chronic disease , whether to continue vaccination depends on themselves

• Subjects with the following conditions may receive vaccination in delayed time or withdraw from the study depending on the judgment of investigator

  1. Acute disease (moderate or severe disease with or without fever) in case of vaccination
  2. Axillary temperature > 37.0 °C

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EV71 vaccine & blood sampling (0, 10,60); This group receive two doses injection of EV71 vaccine (0, 28 days), and three times of blood sampling on day of 0, 10, and 60 respectively for EV71 neutralizing antibody detection.	Biological: EV71 vaccine; Two doses vaccination of EV71vaccine (Intramuscular injection, 0.5ml) with a schedule of 0, 28 days.
Experimental: EV71 vaccine & blood sampling (0, 20,60); This group receive two doses injection of EV71 vaccine (0, 28 days), and three times of blood sampling on day of 0, 20, and 60 respectively for EV71 neutralizing antibody detection.	Biological: EV71 vaccine; Two doses vaccination of EV71vaccine (Intramuscular injection, 0.5ml) with a schedule of 0, 28 days.
Experimental: EV71 vaccine& blood sampling (0, 30, 60); This group receive two doses injection of EV71 vaccine (0, 28 days), and three times of blood sampling on day of 0, 30, and 60 respectively for EV71 neutralizing antibody detection.	Biological: EV71 vaccine; Two doses vaccination of EV71vaccine (Intramuscular injection, 0.5ml) with a schedule of 0, 28 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The seroconversion rate of EV71 neutralizing antibody 30 days after the two doses vaccination	Immunogenicity indicator	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The seroconversion rate of EV71 neutralizing antibody 10, 20 and 30 days after the first dose vaccination	Immunogenicity indicator	10,20,and 30 days
The seropositive rate of EV71 neutralizing antibody 10, 20, 30, and 60 days after the first dose vaccination	Immunogenicity indicator	10, 20,30,and 60 days
GMT and GMT increase fold of EV71 neutralizing antibody 10,20,30,and 60 days after the first dose vaccination	Immunogenicity indicator	10,20，30，and 60 days
Incidence of unsolicited local or systemic adverse events within 3 days after each dose	Safety indicator	3 days
Incidence of unsolicited adverse events within 30 days after each dose	Safety indicator	30 days
Incidence of the serious adverse events within 60 days after the first dose vaccination	Safety indicator	60 days

Collaborators and Investigators

• Sponsor: Sinovac Biotech Co., Ltd
• Collaborators: Zhejiang Provincial Center for Disease Control and Prevention; Shangyu District Center for Disease Control and Prevention

Publications and helpful links

General Publications

• Wang S, Zeng J, Zhang X, Gan Z, Fan J, Chen Y, Liang Z, Hu X, Zeng G, Lv H. Short-term dynamic changes in neutralizing antibodies against enterovirus 71 after vaccination. Hum Vaccin Immunother. 2020 Jul 2;16(7):1595-1601. doi: 10.1080/21645515.2020.1711678. Epub 2020 Jan 24.

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2017
• Primary Completion (Actual): September 15, 2017
• Study Completion (Actual): September 15, 2017

Study Registration Dates

• First Submitted: September 7, 2017
• First Submitted That Met QC Criteria: September 7, 2017
• First Posted (Actual): September 11, 2017

Study Record Updates

• Last Update Posted (Actual): January 2, 2019
• Last Update Submitted That Met QC Criteria: December 28, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Safety; Immunogenicity; Infant; Inactivated Enterovirus Type 71 (EV71) Vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Stomatognathic Diseases; Enterovirus Infections; Picornaviridae Infections; Coxsackievirus Infections; Mouth Diseases; Foot-and-Mouth Disease; Hand, Foot and Mouth Disease
• Other Study ID Numbers: PRO-EV71-4011

Drug and device information, study documents

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