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

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

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.

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.

Inclusion Criteria:

1. 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.
2. Subject's guardians are able and willing to comply with study procedures and provide the signed informed consent.
3. Subject is able and can comply with the requirements of the protocol.
4. Subject with body temperature <= 38℃.

Exclusion Criteria:

1. Subject with previous known Enterovirus 71 (EV71) infection or investigational EV71 vaccination.
2. Subject with a history of herpangina, hand-foot-mouth disease, and acute hemorrhagic conjunctivitis associated with enterovirus infection in the past 30 days.
3. 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.
4. Subject under 2 years old with gestation <34weeks or a birth weight <2200g.
5. History of epilepsy, seizures or non-febrile convulsions that may affect subject participation in the study in the opinion of the investigator.
6. Severe malnutrition or dysgenopathy at the screening visit.
7. Major congenital defects or serious chronic illness, including perinatal brain damage at the screening visit.
8. 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.
9. Bleeding disorder diagnosed by a doctor or significant bruising or hemostatic difficulties with IM injections or blood draws.
10. Any acute febrile illness 3 days prior to administrating the first vaccination.
11. 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).
12. Administration of any vaccine within 14 days prior to each study vaccination.
13. Use of immunoglobulins or any blood products within 3 months prior to vaccination.
14. Chronic administration (defined as > 14 day of continuous use) of systemic immunosuppressants, other systemic immunomodulators, or systemic corticosteroids within 6 months prior to vaccination.
15. Any condition that in the opinion of the investigator may interfere with the evaluation of study objectives.
16. Subject with any confirmed or suspected immunodeficiency.