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

• ClinicalTrials.gov Identifier: NCT01734408
• Recruitment Status: Completed
• First Posted: November 27, 2012
• Last Update Posted: October 23, 2013
• Sponsor: Jiangsu Province Centers for Disease Control and Prevention
• Collaborator: Bejing Vigoo Biological Co., LTD
• Information provided by (Responsible Party): Fengcai Zhu, Jiangsu Province Centers for Disease Control and Prevention

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
EV71-associated Disease	Biological: alum-adjuvant 160U /0.5ml; Biological: alum-adjuvant 320U /0.5ml; Biological: alum-adjuvant 640U /0.5ml; Biological: adjuvant-free 640U /0.5ml; Biological: 0/0.5ml placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 773 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: A Booster Dose of Inactivated Vaccine (Vero Cell) Against EV71 in Chinese Children
• Study Start Date: November 2012
• Actual Primary Completion Date: January 2013
• Actual Study Completion Date: February 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Geometric mean titer (GMT) of anti-EV71 antibodies [ Time Frame: 28 days after vaccination ]
   GMT of anti-EV71 antibodies in serum 28 days after booster dose injection

Secondary Outcome Measures :

1. Safety of EV71 vaccine in healthy children [ Time Frame: 28 days after vaccination ]
   Frequency of systemic and local adverse reactions in healthy children following 28 days after the boosting dose of EV71 vaccine
2. Geometric mean fold increase (GMFI) of anti-EV71 antibodies [ Time Frame: 28 days after vaccination ]
   GMFI of anti-EV71 antibodies in serum 28 days after vaccination
3. Seroconversion of anti-EV71 antibodies [ Time Frame: 28 days after vaccination ]
   Seroconversion of anti-EV71 antibodies in serum 28 days after vaccination

Eligibility Criteria

• Ages Eligible for Study: 21 Months to 51 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

China, Jiangsu

Jiangsu Provincial Center for Diseases Control and Prevention

Nanjing, Jiangsu, China, 210009

Sponsors and Collaborators

Jiangsu Province Centers for Disease Control and Prevention

Bejing Vigoo Biological Co., LTD

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Fengcai Zhu, vice director, Jiangsu Province Centers for Disease Control and Prevention
• ClinicalTrials.gov Identifier: NCT01734408
• Other Study ID Numbers: JSVCT005b
• First Posted: November 27, 2012
• Last Update Posted: October 23, 2013
• Last Verified: October 2013

Keywords provided by Fengcai Zhu, Jiangsu Province Centers for Disease Control and Prevention:

immunogenicity; safety; inactivated EV71 vaccine

Additional relevant MeSH terms:

Aluminum Hydroxide; Aluminum sulfate; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs; Antacids; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents