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

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

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.

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