A Study to Evaluate the Efficacy, Immunogenicity and Safety of an EV71 Vaccine in Healthy Infants and Children

Study Overview
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Brief Summary
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The objectives of this study are to evaluate the EV71vaccine efficacy, immune response and safety profiles after two injections of the cell culture-based inactivated EV71 vaccine with adjuvant Al(OH)3 administrated in pediatric population aged 2 months to 6 years old.

Detailed Description
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The clinical trial designed in this Study is a placebo-controlled, double-blinded Phase III and is aimed to evaluate the vaccine efficacy, safety, immunogenicity and immune persistence of cell culture-based inactivated EV71 vaccine in children age of 2 months to <6 years old. Two doses of Alum-adjuvanted 1.0 μg per dose of EV71 vaccine candidate will be administrated to subjects. The efficacy will be evaluated within a two year period after receiving 2-regimen vaccination by comparing the EV71-associated disease rates between the vaccine and placebo groups. Whereas, the immunogenicity will be assessed on Day 56 and Day 196, and the immune persistence will be evaluated on Day 392. Safety will be followed up to Day 392.

Official Title
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A Phase III, Multiple-center, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy, Immunogenicity, and Safety of an Adjuvanted, Inactivated Enterovirus 71 (EV71) Vaccine in Healthy Infants and Children

Conditions
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Enterovirus Infections

Intervention / Treatment
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* Biological: EV71 vaccine
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy children aged from 2 months to 6 years old (i.e. >= 2 months old and < 7 years old) at the time of first vaccination. Subject's guardians are able and willing to comply with study procedures and provide the signed informed consent. Subject is able and can comply with the requirements of the protocol. Subject with body temperature <= 38℃. Exclusion Criteria: Subject with previous known Enterovirus 71 (EV71) infection or investigational EV71 vaccination. Subject with a history of herpangina, hand-foot-mouth disease, and acute hemorrhagic conjunctivitis associated with enterovirus infection in the past 30 days. Subject with a history of hypersensitivity to vaccines, or a history of allergic disease or reactions likely to be exacerbated by any component of the vaccine. Subject under 2 years old with gestation <34weeks or a birth weight <2200g. History of epilepsy, seizures or non-febrile convulsions that may affect subject participation in the study in the opinion of the investigator. Severe malnutrition or dysgenopathy at the screening visit. Major congenital defects or serious chronic illness, including perinatal brain damage at the screening visit. Subject diagnosed of having autoimmune disease (e.g., celiac disease, type I diabetes, lupus (SLE), juvenile dermatomyositis, scleroderma, juvenile idiopathic arthritis (JIA), immune (or idiopathic) thrombocytopenia purpura) that may affect subject participation in the study in the opinion of the investigator. Bleeding disorder diagnosed by a doctor or significant bruising or hemostatic difficulties with IM injections or blood draws. Any acute febrile illness 3 days prior to administrating the first vaccination. Use of any investigational product (including drug, vaccine) within 30 days prior to vaccination or planned use during Visit 1 to Visit 4 (Day 0 to Day 196). Administration of any vaccine within 14 days prior to each study vaccination. Use of immunoglobulins or any blood products within 3 months prior to vaccination. Chronic administration (defined as > 14 day of continuous use) of systemic immunosuppressants, other systemic immunomodulators, or systemic corticosteroids within 6 months prior to vaccination. Any condition that in the opinion of the investigator may interfere with the evaluation of study objectives. Subject with any confirmed or suspected immunodeficiency.

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 71 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EV71 Vaccine<br> | Biological: EV71 vaccine<br>* EV71 vaccine ([1 μg total protein + adjuvant 150 μg AI(OH)3] per dose) Two vaccinations at 28 days apart<br>|
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* Placebo ([ adjuvant 150 μg AI(OH)3] per dose) Two vaccinations at 28 days apart<br>|

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 after the second vaccination. | Evaluate the efficacy of EV71 vacccine against HFMD caused by EV71 | From 28 days after the second vaccination to two year | 
| Serum neutralizing antibody titers (NT) induced by the EV71 vaccine | Evaluate the immunogenicity by the response rate | 28 days after the second vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence rate of the severe complications and hospitalization of EV71 associated HFMD/HA disease after the second vaccination. | Evaluate the efficacy of vaccination against the severe complications, including neurologic, pulmonary edema, and cardiorespiratory failure, of EV71 associated HFMD/HA diseases after completion of full vaccination. Evaluate the efficacy of vaccination against the hospitalization of EV71 associated HFMD/HA diseases after completion of full vaccination. | From 28 days after the second vaccination to two year | 
| Serum neutralizing antibody titers (NT) induced by the EV71 vaccine | Evaluate the immunogenicity of EV71 vaccine with two-dose regimen. Evaluate the immune persistence of EV71 vaccine with two-dose regimen. Evaluate lot-to-lot consistency by comparing the immunogenicity induced by 3 independent EV71 vaccines. | Day 0,56,196,and 392 | 
| Adverse events of EV71 vaccine | Occurrence and severity of solicited injection site relations and general reactions within 7 days following each injection. Occurrence and severity of unsolicited adverse events within 28 days following each injection. Occurrence and relations with vaccination of some special AE during the 6-months follow-up period (up to Day 196). Occurrence and relations with vaccination of serious adverse events (SAEs) during the one year follow-up period (up to Day 392). | Day 0 to Day 392 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Foot-and-Mouth Disease, Vaccines, Hand, foot and mouth Disease, EV71 vaccine