An Efficacy Trial in Inactivated Enterovirus Type 71 (EV71) Vaccine

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy, immunogenicity and safety of EV71 Vaccines in preventing Hand, Foot and Mouth disease caused by EV71 in a total 10,000 healthy infants volunteers aged from 6 to 35months old.

Detailed Description
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The phase II study of inactivated vaccine (vero cell) against EV71 has completed on Dec 2011 in China. The data from the phase I and II study suggested that the inactivated EV71 vaccine had a clinically acceptable safety and good immunogenicity for healthy Chinese infants. In order to evaluate the efficacy of the vaccine against Hand, Foot and Mouth disease caused by EV71, and to further explore the safety profile of this vaccine in expending infant population, a phase III clinical trial is planed to conduct.

Official Title
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A Multicentered, Double - Blind, Randomized, and Placebo - Controlled Clinical Trial With Inactivated Enterovirus Type 71 (EV71) Vaccines

Conditions
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Hand, Foot and Mouth Disease

Intervention / Treatment
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* Biological: 400U /0.5ml EV71 vaccine
* Biological: 0/0.5ml placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males and females, aged from 6 months to 11 years old Health is determined by medical history, physical examination, laboratory examination and clinical judgment of the investigator Provided legal identification for the sake of recruitment Subjects and/or parent(s)/legal guardian(s) are able to understand and sign informed consents Exclusion Criteria: History of Hand-foot-mouth Disease Subject that has allergic history of vaccine, or allergic to any ingredient of vaccine Serious adverse reactions to vaccines such as anaphylaxis, hives, respiratory difficulty, angioedema, or abdominal pain Congenital malformations or developmental disorders, genetic defects, or severe malnutrition Epilepsy, seizures or convulsions history, or family history of mental illness Autoimmune disease or immunodeficiency, or parents, brothers and sisters have autoimmune diseases or immunodeficiency History of asthma, angioedema, diabetes or malignancy History of thyroidectomy or thyroid disease that required medication within the past 12 months Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws Asplenia, functional asplenia or any condition resulting in the absence or removal the spleen Acute illness or acute exacerbation of chronic disease within the past 7 days Any history of immunosuppressive medications or cytotoxic medications or inhaled corticosteroids within the past six months (with the exception of corticosteroid nasal spray for allergic rhinitis or topical corticosteroids for an acute uncomplicated dermatitis) History of any blood products within 3 months Administration of any live attenuated vaccine within 14 days Administration of subunit or inactivated vaccines ,e.g., pneumococcal vaccine, or allergy treatment within 7 days Axillary temperature > 37.0 centigrade before vaccination Abnormal laboratory parameters before vaccination Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent

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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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 400U /0.5ml in infants<br>inactivated vaccine(vero cell) against EV71 of 400U /0.5ml in 5000 infants aged 6-35 months old on day0,28 | Biological: 400U /0.5ml EV71 vaccine<br>* inactivated vaccine (vero cell) against EV71 of 400U /0.5ml, two doses, 28 days interval<br>* Other names: EV71 vaccine;|
| Placebo Comparator: 0/0.5ml placebo in infants<br>0/0.5ml placebo in 5000 infants aged 6-35 months old on day0,28 | Biological: 0/0.5ml placebo<br>* 0/0.5ml placebo, two doses, 28 days interval<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence rate of Hand, Foot and Mouth disease caused by EV71 within one year observation period after the second vaccination | to evaluate the efficacy of EV71 vacccine against HFMD caused by EV71 | From 28 days after the second vaccination to one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The GMT of anti-EV71 antibodies in serum after second vaccination | to evaluate the GMT of anti-EV71 antibodies in serum 28 days after second vaccination | 28 days after first vaccination | 
| The GMT of anti-EV71 antibodies in serum 7 and 13 months after second vaccination | to evaluate the immune persistence of anti-EV71 antibodies in serum | 7 and 13 months after second vaccination | 
| Frequency of systemic and local adverse reactions after the first vaccination | Frequency of systemic and local adverse reactions in healthy infants following first doses of EV71 vaccine | 28 days after the first vaccination | 
| Frequency of systemic and local adverse reactions after the second vaccination | Frequency of systemic and local adverse reactions in healthy infants following second doses of EV71 vaccine | 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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EV71 vaccine, HFMD, efficacy, EV71 associated disease