Immunogenicity and Safety of Three Consecutive Lots of a New 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 immunogenicity and safety of three consecutive lots of EV71 Vaccines in healthy infants volunteers aged from 6 months to 5 years old.

Detailed Description
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The data from the phase I and II study suggested that the inactivated EV71 vaccine (vero cell) had a clinically acceptable safety and good immunogenicity for healthy Chinese infants. The phase III study of inactivated vaccine has initiated on Jan 2012 in China. Over 10,000 healthy infants have revieved the vaccines and no unexpected severe adverse reactions were reported. According to the requirement of SFDA (China), the sponsor should also provide the evidence for the consistency of three consecutive lots of EV71 Vaccines before the application for the market. Thus, a clinical trial to evaluate the immunogenicity and safety of three consecutive lots of EV71 Vaccines in healthy infants volunteers is planed to conduct.

Official Title
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Immunogenicity and Safety of Three Consecutive Lots of a New Inactivated Enterovirus Type 71 (EV71) Vaccine: A Double-blind, Randomized and Controlled Trial

Conditions
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Hand, Foot and Mouth Disease

Intervention / Treatment
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* Biological: three consecutive lots of EV71 vaccine
* Biological: 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: 5 Years

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: Lot 1<br>inactivated vaccine (Lot 1) against EV71 of 400U /0.5ml in 350 infants aged 6 months to 5 years old on day 0,28 | Biological: three consecutive lots of EV71 vaccine<br>* inactivated vaccine (vero cell) against EV71 of 400U /0.5ml, two doses, 28 days interval<br>* Other names: Vaccine groups;|
| Experimental: Lot 2<br>inactivated vaccine (Lot 2) against EV71 of 400U /0.5ml in 350 infants aged 6 months to 5 years old on day 0,28 | Biological: three consecutive lots of EV71 vaccine<br>* inactivated vaccine (vero cell) against EV71 of 400U /0.5ml, two doses, 28 days interval<br>* Other names: Vaccine groups;|
| Experimental: Lot 3<br>inactivated vaccine (Lot 3) against EV71 of 400U /0.5ml in 350 infants aged 6 months to 5 years old on day 0,28 | Biological: three consecutive lots of EV71 vaccine<br>* inactivated vaccine (vero cell) against EV71 of 400U /0.5ml, two doses, 28 days interval<br>* Other names: Vaccine groups;|
| Placebo Comparator: Placebo<br>Placebo in 350 infants aged 6 months to 5 years old on day 0,28 | Biological: placebo<br>* placebo, two doses, 28 days interval<br>* Other names: Control group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The GMT of anti-EV71 antibodies in serum 28 days after the two-dose regimen | to evaluate the immunogenicity of anti-EV71 antibodies in serum 28 days after second vaccination | 28 days after first vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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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consistency of three consecutive lots, 71 vaccine, HFMD, immunogenicity