A Booster Dose of Inactivated Vaccine (Vero Cell) Against EV71 in Chinese Children

Hand, foot, and mouth disease (HFMD) is a common viral illness in infants and children caused by viruses that belong to the enterovirus genus of the picornavirus family. Although most HFMD cases do not result in serious complications, outbreaks of HFMD caused by enterovirus 71 (EV71) can present with a high rate of neurological complications, including meningoencephalitis, pulmonary complications, and can even cause infant death. HFMD caused by EV71 has become a major emerging infectious disease in Asia and the highly pathogenic potential of EV71 clearly requires the attention of world medical community.

The phase II study of inactivated vaccine (vero cell) against EV71 has completed last month in Jiangsu Province in China. The data from the phase II study suggested that the inactivated EV71 vaccine had a clinically acceptable safety and good immunogenicity for healthy Chinese children and infants. But the antibody titer against EV71 was found decreased significantly at month 8 compared to that at day 56. Considering the similar dynamic trend had also been found in the antibody against poliovirus induced by polio vaccines, and whose immunization schedule contains a booster dose administrated at 1 to 1.5 year after the first 3 doses of fundamental immunity. In order to find a better immunization schedule for children, the investigators decided to perform this booster immunity trial among these children who had received two doses of EV71 vaccines (around one year after the fundamental immunity). The investigators do the recruitment among these children who had participated in the previous phase II trial and received EV71 vaccines, and randomize them in a ratio of 2:1 to receive either a booster dose of EV71 vaccines or placebo.

Study Overview

• Status: Completed
• Conditions: EV71-associated Disease
• Intervention / Treatment: Biological: alum-adjuvant 160U /0.5ml; Biological: 0/0.5ml placebo; Biological: alum-adjuvant 320U /0.5ml; Biological: alum-adjuvant 640U /0.5ml; Biological: adjuvant-free 640U /0.5ml

• Study Type: Interventional
• Enrollment (Actual): 773
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Jiangsu Provincial Center for Diseases Control and Prevention

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 4 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Had participated in the previous phase II trial and received at least 1 dose of EV71 vaccine.
• Healthy children as established by medical history and clinical examination
• The subjects' guardians are able to understand and sign the informed consent
• Subjects who can and will comply with the requirements of the protocol
• Subjects with temperature <=37.0°C on axillary setting

Exclusion Criteria:

• Had participated in the previous phase II trial and received placebo.
• Subject who has a medical history of EV71-associated disease with specific laboratory evidence
• <= 37 weeks gestation
• Subjects with a birth weight <2.5 kg
• Subject that has a medical history of any of the following: allergic history, or allergic to any ingredient of vaccine
• Family history of seizures or progressive neurological disease
• Family history of congenital or hereditary immunodeficiency
• Severe malnutrition or dysgenopathy
• Major congenital defects or serious chronic illness, including perinatal brain damage
• Autoimmune disease
• Bleeding disorder diagnosed by a doctor or significant bruising or bleeding difficulties with IM injections or blood draws
• Any acute infections in last 7 days
• Any prior administration of immunodepressant or corticosteroids in last 6month
• Any prior administration of blood products in last 3 month
• Any prior administration of other research medicines in last 1 month
• Any prior administration of attenuated live vaccine in last 14 days
• Any prior administration of subunit or inactivated vaccines in last 7 days, such as pneumococcal vaccine
• Under the anti-TB prevention or therapy
• Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: alum-adjuvant 160U /0.5ml EV71 vaccine; A booster dose of alum-adjuvant 160U /0.5ml EV71 vaccine in 160 children whom had received two doses of alum-adjuvant 160U/0.5ml EV71 vaccines one year before.	Biological: alum-adjuvant 160U /0.5ml; inactivated vaccine (vero cell) alum-adjuvant 160U /0.5ml EV71 vaccine
Placebo Comparator: placebo A; A 0/0.5ml placebo in 80 children whom had received two doses of alum-adjuvant 160U/0.5ml EV71 vaccines one year before.	Biological: 0/0.5ml placebo; 0/0.5ml placebo
Experimental: alum-adjuvant 320U /0.5ml EV71 vaccine; A booster dose of alum-adjuvant 320U /0.5ml EV71 vaccine in 160 children whom had received two doses of alum-adjuvant 320U/0.5ml EV71 vaccines one year before.	Biological: alum-adjuvant 320U /0.5ml; inactivated vaccine (vero cell) alum-adjuvant 320U /0.5ml EV71 vaccine
Placebo Comparator: placebo B; A 0/0.5ml placebo in 80 children whom had received two doses of alum-adjuvant 320U/0.5ml EV71 vaccines one year before.	Biological: 0/0.5ml placebo; 0/0.5ml placebo
Experimental: alum-adjuvant 640U /0.5ml EV71 vaccine; A booster dose of alum-adjuvant 640U /0.5ml EV71 vaccine in 160 children whom had received two doses of alum-adjuvant 640U/0.5ml EV71 vaccines one year before.	Biological: alum-adjuvant 640U /0.5ml; inactivated vaccine (vero cell) alum-adjuvant 640U /0.5ml EV71 vaccine
Placebo Comparator: placebo C; A 0/0.5ml placebo in 80 children whom had received two doses of alum-adjuvant 640U/0.5ml EV71 vaccines one year before.	Biological: 0/0.5ml placebo; 0/0.5ml placebo
Experimental: adjuvant-free 640U /0.5ml EV71 vaccine; A booster dose of adjuvant-free 640U /0.5ml EV71 vaccine in 160 children whom had received two doses of adjuvant-free 640U/0.5ml EV71 vaccines one year before.	Biological: adjuvant-free 640U /0.5ml; inactivated vaccine (vero cell) adjuvant-free 640U /0.5ml EV71 vaccine
Placebo Comparator: placebo D; A 0/0.5ml placebo in 80 children whom had received two doses of adjuvant-free 640U/0.5ml EV71 vaccines one year before.	Biological: 0/0.5ml placebo; 0/0.5ml placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric mean titer (GMT) of anti-EV71 antibodies	GMT of anti-EV71 antibodies in serum 28 days after booster dose injection	28 days after vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of EV71 vaccine in healthy children	Frequency of systemic and local adverse reactions in healthy children following 28 days after the boosting dose of EV71 vaccine	28 days after vaccination
Geometric mean fold increase (GMFI) of anti-EV71 antibodies	GMFI of anti-EV71 antibodies in serum 28 days after vaccination	28 days after vaccination
Seroconversion of anti-EV71 antibodies	Seroconversion of anti-EV71 antibodies in serum 28 days after vaccination	28 days after vaccination

Collaborators and Investigators

• Sponsor: Jiangsu Province Centers for Disease Control and Prevention
• Collaborators: Bejing Vigoo Biological Co., LTD

Publications and helpful links

General Publications

• Shenyu W, Jingxin L, Zhenglun L, Xiuling L, Qunying M, Fanyue M, Hua W, Yuntao Z, Fan G, Qinghua C, Yuemei H, Xin Y, Huijie G, Fengcai Z. A booster dose of an inactivated enterovirus 71 vaccine in chinese young children: a randomized, double-blind, placebo-controlled clinical trial. J Infect Dis. 2014 Oct 1;210(7):1073-82. doi: 10.1093/infdis/jiu113. Epub 2014 Mar 12.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: November 22, 2012
• First Submitted That Met QC Criteria: November 26, 2012
• First Posted (Estimate): November 27, 2012

Study Record Updates

• Last Update Posted (Estimate): October 23, 2013
• Last Update Submitted That Met QC Criteria: October 21, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: safety; immunogenicity; inactivated EV71 vaccine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunologic Factors; Gastrointestinal Agents; Adjuvants, Immunologic; Antacids; Aluminum Hydroxide; Aluminum sulfate
• Other Study ID Numbers: JSVCT005b