A Clinical Trial to Assess the Efficacy and Safety of an Inactivated Vaccine (Vero Cell) Against EV71 in Chinese Children Aged 6-35 Months

Study Overview
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Brief Summary
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Since its discovery in 1969, enterovirus 71 (EV71) has been recognised as a frequent cause of epidemics of hand-foot-mouth disease (HFMD) associated with severe neurological sequelae in a small proportion of cases. There has been a significant increase in EV71 epidemic activity throughout the Asia-Pacific region since 1997. Recent HFMD epidemics in this region have heen associated with a severe from of brainstem encephalitis associated with pulmonary oedema and high case-fatality rates. The data from the phase 1 and 2 trials suggested that the inactivated EV71 vaccine had a clinically acceptable safety and good immunogenicity for healthy Chinese children and infants. According to the immunogenicity and safety results, the 320U with adjuvant with immunizing schedule of two doses (per 28 day) will be applied in phase 3 clinical trial.

Official Title
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A Multiple-center Randomized Double-blind Placebo-controlled Phase 3 Clinical Trial to Assess the Efficacy and Safety of an Inactivated Vaccine (Vero Cell) Against EV71 in Chinese Children Aged 6-35 Months

Conditions
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Hand, Foot and Mouth Disease, Herpangina, Other EV71-associated Diseases

Intervention / Treatment
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* Biological: inactivated vaccine (Vero Cell) against EV71
* Biological: 0/0.5ml placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Only subjects fulfilling all of the following criteria will be eligible for the study: Healthy children aged from 6 to 35 months old General good health as established by medical history and physical examination The subjects' guardians are able to understand and sign the informed consent Had never received the vaccine against EV71 The subjects' guardians allow to comply with the requirements of the protocol Available for all visits scheduled in this study Subjects with temperature <=37.0°C on axillary setting Exclusion Criteria: Subjects will not be eligible for the study if any of the following criteria is met: Subject who has a medical history of HFMD 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 hypogenesis 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 Asplenia, functional asplenia, or splenic excision History of asthma, angioneurotic edema, diabetes or malignant tumour History of thyroidectomy, or thyroid disease in last 12 months Any acute infections in last 7 days Any prior administration of immunodepressant or corticosteroids in last 6 months Any prior administration of blood products in last 3 months Any prior administration of other research vaccines or medicines 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 Subjects with temperature >37.0°C on axillary setting Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives Exclusion Criteria for the second dose: Subjects will not be eligible for the second dose if any of following adverse events happened after the first dose. They can continue other process of the study without the second dose vaccination according to the opinion of the investigator. Had any serious adverse events related to the first dose of inactivated vaccine (vero cell) against EV71 within 7 days Hypersensitivity reactions after vaccination (including urticaria/rashes that occur within 30 minutes after inoculation) Anaphylaxis after vaccination Any confirmed or suspected autoimmune disease or immune deficiency diseases, including human immunodeficiency virus (HIV) infection Any condition that in the opinion of the investigator, or IRB

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 35 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: vaccine against EV71<br>Inactivated vaccine (Vero Cell) against EV71 of 320U /0.5ml in 5000 children aged 6-35 months on day0, 28 | Biological: inactivated vaccine (Vero Cell) against EV71<br>* inactivated vaccine (vero cell) against EV71, 320U /0.5ml, two doses, on day0, 28<br>|
| Placebo Comparator: placebo<br>0/0.5ml placebo in 5000 children aged 6-35 months on day0, 28 | Biological: 0/0.5ml placebo<br>* 0/0.5ml placebo, two doses, on day0, 28<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the incidence density of the EV71-associated diseases in the vaccine group and placebo group. | compare the incidence density of the EV71-associated diseases between the vaccine group and placebo group in Chinese children aged 6-35 months. | begin at day 56 up to 14 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the frequency of all the adverse events in vaccine group and placebo group. | compare frequency of all the solicited events, unsolicited adverse events and serious adverse events between vaccine group and placebo group. | up to 14 months | 
| Seropositive rate of the vaccine group | calculate the seropositive rate of the vaccine group in Chinese children aged 6-35 months at month 8 after first vaccination. | 8 months after first vaccination | 
| Seroconversion rate of the vaccine group | calculate the seroconversion rate of the vaccine group in Chinese children aged 6-35 months at month 8 after first vaccination. | 8 months after first vaccination | 
| GMT of the vaccine group | calculate the geometric mean titre (GMT) of the vaccine group in Chinese children aged 6-35 months at month 8 after first vaccination. | 8 months after first vaccination | 
| Seropositive rate of the vaccine group | calculate the seropositive rate of the vaccine group in Chinese children aged 6-35 months at month 14 after first vaccination. | 14 months after first vaccination | 
| Seroconversion rate of the vaccine group | calculate the seroconversion rate of the vaccine group in Chinese children aged 6-35 months at month 14 after first vaccination. | 14 months after first vaccination | 
| GMT of the vaccine group | calculate the geometric mean titre (GMT) of the vaccine group in Chinese children aged 6-35 months at month 14 after first vaccination. | 14 months after first vaccination | 
| Seropositive rate of the vaccine group and placebo group | compare the seropositive rate of the vaccine group and placebo group in healthy children aged 6-35 months. | 28 days after the second vaccination | 
| Seroconversion rate of the vaccine group and placebo group | compare the Seroconversion rate of the vaccine group and placebo group in healthy children aged 6-35 months. | 28 days after the second vaccination | 
| GMT of the vaccine group and placebo group | compare the geometric mean titre (GMT) of the vaccine group and placebo group in healthy children aged 6-35 months. | 28 days after the second vaccination | 
| GMI of the vaccine group and placebo group | compare the geometric mean fold increase (GMFI) of the vaccine group and placebo group in healthy children aged 6-35 months. | 28 days after the second vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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efficacy, safety, inactivated vaccine (Vero Cell) against EV71, EV71-associated diseases