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

Study Overview
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Brief Summary
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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.

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

Conditions
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EV71-associated Disease

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Months
Maximum Age: 51 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: alum-adjuvant 160U /0.5ml EV71 vaccine<br>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<br>* inactivated vaccine (vero cell) alum-adjuvant 160U /0.5ml EV71 vaccine<br>|
| Placebo Comparator: placebo A<br>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<br>* 0/0.5ml placebo<br>|
| Experimental: alum-adjuvant 320U /0.5ml EV71 vaccine<br>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<br>* inactivated vaccine (vero cell) alum-adjuvant 320U /0.5ml EV71 vaccine<br>|
| Placebo Comparator: placebo B<br>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<br>* 0/0.5ml placebo<br>|
| Experimental: alum-adjuvant 640U /0.5ml EV71 vaccine<br>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<br>* inactivated vaccine (vero cell) alum-adjuvant 640U /0.5ml EV71 vaccine<br>|
| Placebo Comparator: placebo C<br>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<br>* 0/0.5ml placebo<br>|
| Experimental: adjuvant-free 640U /0.5ml EV71 vaccine<br>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<br>* inactivated vaccine (vero cell) adjuvant-free 640U /0.5ml EV71 vaccine<br>|
| Placebo Comparator: placebo D<br>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<br>* 0/0.5ml placebo<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunogenicity, safety, inactivated EV71 vaccine