Immunity and Safety of Inactivated Enterovirus 71 Vaccine Post-marketing Among Children Aged 6-35 Months in China

Three Batches Consistency, Immunity Duration and Safety of Inactivated Enterovirus 71 Vaccine Post-marketing Among Children Aged 6-35 Months in China

This study evaluates three batches consistency, immunity duration and safety of inactivated Enterovirus 71(EV-A71) vaccine(vero cell) post-marketing among children aged 6-35months in China.3000 subjects will be recruited in this study, of who 1500 subjects will be randomly assigned in a ratio of 1:1:1 to receive one of the three batches of EV-A71 vaccines manufactured by 40L capacity reactor, other 1500 subjects will be randomly assigned in a ratio of 1:1:1 to receive one of the three batches of EV-A71 vaccines manufactured by 150L capacity reactor. Vaccine wil be administrated according to a two doses of schedule given at day 0 and 28. Sample will be collected at day 0, day 56 and at month 13 after vaccinaiton.

Study Overview

• Status: Completed
• Conditions: Hand, Foot and Mouth Disease
• Intervention / Treatment: Biological: The first batch of inactivated EV-A71 vaccine (vero cell) producted by 40 L reactor; Biological: The second batch of inactivated EV-A71 vaccine (vero cell) producted by 40 L reactor; Biological: The third batch of inactivated EV-A71 vaccine (vero cell) producted by 40 L reactor; Biological: The first batch of inactivated EV-A71 vaccine (vero cell) producted by 150 L reactor; Biological: The second batch of inactivated EV-A71 vaccine (vero cell) producted by 150 L reactor; Biological: The third batch of inactivated EV-A71 vaccine (vero cell) proudected by 150 L reactor

• Study Type: Interventional
• Enrollment (Actual): 3000
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Nanjing, China
    • Fengcai Zhu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy children aged 6-35 months
• Subjects who have been clinically judged to be healthy by the researcher after being asked about the medical history and related physical examination
• The subjects' guardians agree the requirements of the protocol and the relevant follow up visits
• The subjects' guardians agree and sign the informed consent
• Subjects who have no relocation or long-term travel plan within one year and are able to comply with the requirements of the clinical trial protocol.

Exclusion Criteria:

• Subject who has a medical history of HFMD caused by EV71 or has been vaccinated with EV71 vaccine
• Subject that has a history of allergies to vaccines or vaccine ingredients, and has serious side effects on vaccines, such as allergies, urticaria, dyspnea, vascular neuroedema or abdominal pain
• Subject who has congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc.
• Subject who has a history of epilepsy, convulsion or convulsion, or a family history of mental illness
• Subject who has autoimmune disease or immune deficiency, or whose parents and siblings have autoimmune disease or immune deficiency
• Subject who has a history of asthma, vascular and neuroedema, diabetes or malignant tumor
• Subject who has a thyroid resection history, or received treatment due to thyroid disease in the past 12 months
• Subject who has an abnormal coagulation function (such as coagulation factor deficiency, coagulant disease, platelet abnormality) or obvious bruising or clotting disorder which was diagnosed by doctors.
• Asplenia, functional asplenia, or splenectomy due to any circumstances
• Acute onset of various acute or chronic diseases in the last 7 days
• Immunosuppressant therapy, antiallergic therapy, cytotoxicity therapy, inhaled corticosteroids (excluding corticosteroid spray therapy for allergic rhinitis, surface corticosteroid therapy for acute non-dermatitis) in the past 6 months
• Any prior administration of blood products in last 3 months
• Any prior administration of other research medicines or vaccines in last 1 month
• Any prior administration of attenuated live vaccine in last 15 days
• Any prior administration of subunit or inactivated vaccines in last 7 days
• Under the anti-TB prevention or therapy
• Underarm temperature > 37.0 ℃ for fever before vaccination
• Other factors that are not suitable for clinical trials according to the judgment of researchers

Exclusion Criteria for the second dose:

• Have severe allergic reaction after first dose
• Have severe adverse reactions related to first dose
• Any situation meet the exclusion criteria stated in the exclusion criteria for first dose
• Acute infection or illness
• Other factors that are not suitable for clinical trials according to the judgment of researchers

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: the first batch vaccine producted by 40 L reactor; 500 subjects will be randomly received the first batch vaccine producted by 40 L reactor	Biological: The first batch of inactivated EV-A71 vaccine (vero cell) producted by 40 L reactor; 500 subjects will be randomized to receive the first batch of inactivated EV-A71 vaccine (vero cell) producted by 40 L reactor
Experimental: the second batch vaccine producted by 40 L reactor; 500 subjects will be randomly received the second batch vaccine producted by 40 L reactor	Biological: The second batch of inactivated EV-A71 vaccine (vero cell) producted by 40 L reactor; 500 subjects will be randomized to receive the second batch of inactivated EV-A71 vaccine (vero cell) producted by 40 L reactor
Experimental: the third batch vaccine producted by 40 L reactor; 500 subjects will be randomly received the third batch vaccine producted by 40 L reactor	Biological: The third batch of inactivated EV-A71 vaccine (vero cell) producted by 40 L reactor; 500 subjects will be randomized to receive the third batch of inactivated EV-A71 vaccine (vero cell) producted by 40 L reactor
Experimental: the first batch vaccine producted by 150 L reactor; 500 subjects will be randomly received the first batch vaccine producted by 150 L reactor	Biological: The first batch of inactivated EV-A71 vaccine (vero cell) producted by 150 L reactor; 500 subjects will be randomized to receive the first batch of inactivated EV-A71 vaccine (vero cell) producted by 150 L reactor
Experimental: the second batch vaccine producted by 150 L reactor; 500 subjects will be randomly received the second batch vaccine producted by 150 L reactor	Biological: The second batch of inactivated EV-A71 vaccine (vero cell) producted by 150 L reactor; 500 subjects will be randomized to receive the second batch of inactivated EV-A71 vaccine (vero cell) producted by 150 L reactor
Experimental: the third batch vaccine proudected by 150 L reactor; 500 subjects will be randomly received the third batch vaccine producted by 150 L reactor	Biological: The third batch of inactivated EV-A71 vaccine (vero cell) proudected by 150 L reactor; 500 subjects will be randomized to receive the third batch of inactivated EV-A71 vaccine (vero cell) proudected by 150 L reactor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Consistency of different batches for geometric mean titre(GMT) after vaccination	Consistency of different batches for GMT of EV-A71 neutralizing antibody on 56 day after vaccination	56 days after vaccination
Incidence and severity of adverse reactions/adverse events after each dose	Incidence and severity of adverse reactions/adverse events within 1 month after each dose	1 month after each dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of sever adverse events after vaccination	Incidence of sever adverse events within 13 months after vaccination	13 months after vaccination
GMTof EV-A71 neutralizing antibody on day 56 after vaccination	GMTof EV-A71 neutralizing antibody on day 56 after vaccination for different batchs	56 days after vaccination
Positive rate of EV-A71 neutralizing antibody on day 56 after vaccination	Positive rate of EV-A71 neutralizing antibody on day 56 after vaccination for different batchs	56 days after vaccination
Seroconversion rate of EV-A71 neutralizing antibody on day 56 after vaccination	Seroconversion rate of EV-A71 neutralizing antibody on day 56 after vaccination for different batchs	56 days after vaccination
Geometric Mean Fold Increase(GMFI) of EV-A71 neutralizing antibody on day 56 after vaccination	Geometric Mean Fold Increase(GMFI) of EV-A71 neutralizing antibody on day 56 after vaccination for different batchs	56 days after vaccination
GMTof EV-A71 neutralizing antibody on month 13 after vaccination	GMTof EV-A71 neutralizing antibody on month 13 after vaccination for different batchs	13 months after vaccination
Positive rate of EV-A71 neutralizing antibody on month 13 after vaccination	Positive rate of EV-A71 neutralizing antibody on month 13 after vaccination for different batchs	13 months after vaccination

Collaborators and Investigators

• Sponsor: Jiangsu Province Centers for Disease Control and Prevention
• Collaborators: Wuhan Institute of Biological Products Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Actual): May 1, 2020
• Study Completion (Actual): May 1, 2020

Study Registration Dates

• First Submitted: March 26, 2019
• First Submitted That Met QC Criteria: March 27, 2019
• First Posted (Actual): March 28, 2019

Study Record Updates

• Last Update Posted (Actual): May 24, 2021
• Last Update Submitted That Met QC Criteria: May 21, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• 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; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: JSVCT048-2

Drug and device information, study documents

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