A Booster Dose of Inactivated Vaccine (Vero Cell) Against EV71 in Chinese Children - Full Text View

Purpose

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	Intervention	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 Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Prevention
Official Title:	A Booster Dose of Inactivated Vaccine (Vero Cell) Against EV71 in Chinese Children

Resource links provided by NLM:

Drug Information available for: Algeldrate Alum, potassium Aluminum sulfate anhydrous Aluminum sulfate

U.S. FDA Resources

Further study details as provided by Jiangsu Province Centers for Disease Control and Prevention:

Primary Outcome Measures:

Geometric mean titer (GMT) of anti-EV71 antibodies [ Time Frame: 28 days after vaccination ] [ Designated as safety issue: No ]
GMT of anti-EV71 antibodies in serum 28 days after booster dose injection

Secondary Outcome Measures:

Safety of EV71 vaccine in healthy children [ Time Frame: 28 days after vaccination ] [ Designated as safety issue: Yes ]
Frequency of systemic and local adverse reactions in healthy children following 28 days after the boosting dose of EV71 vaccine
Geometric mean fold increase (GMFI) of anti-EV71 antibodies [ Time Frame: 28 days after vaccination ] [ Designated as safety issue: No ]
GMFI of anti-EV71 antibodies in serum 28 days after vaccination
Seroconversion of anti-EV71 antibodies [ Time Frame: 28 days after vaccination ] [ Designated as safety issue: No ]
Seroconversion of anti-EV71 antibodies in serum 28 days after vaccination

Enrollment:	773
Study Start Date:	November 2012
Study Completion Date:	February 2013
Primary Completion Date:	January 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility

Ages Eligible for Study:	21 Months to 51 Months
Genders Eligible for Study:	Both
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
Had never received the vaccine against EV71
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01734408

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

No publications provided

Responsible Party:	Fengcai Zhu, vice director, Jiangsu Province Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:	NCT01734408 History of Changes
Other Study ID Numbers:	JSVCT005b
Study First Received:	November 22, 2012
Last Updated:	May 7, 2013
Health Authority:	China: Food and Drug Administration

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

immunogenicity
safety
inactivated EV71 vaccine

Additional relevant MeSH terms:

Adjuvants, Immunologic
Aluminum Hydroxide
Aluminum sulfate
Immunologic Factors

Physiological Effects of Drugs
Pharmacologic Actions
Antacids
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 21, 2013