Hand, Foot and Mouth Disease
Conditions
Keywords
Enterovirus 71, Inactivated enterovirus 71 vaccine
Brief summary
This study is a randomized, blinded study to evaluate the lot-to-lot consistency of immunogenicity, safety, and immune persistence of three consecutive manufacturing lots of EV71 vaccine, in 1500 children aged 6-35 months. The primary immunogenicity endpoint is the anti-EV71 neutralizing antibody geometric mean titer (GMT) 30 days after the final dose. The secondary immunogenicity endpoints are the geometric mean fold increases and seroconversion rates of anti-EV71 neutralizing antibodies 30 days after the final dose. The immune persistence endpoints are the seropositive rates as well as GMT of anti-EV71 neutralizing antibodies 12 and 24 months after the final dose. The safety endpoints are the number of adverse events/reactions within 30 minutes after each dose, the number of solicited adverse events/reactions within 7 days after each dose, the number of unsolicited adverse events/reactions within 30 days after each dose, and the number of serious adverse events (SAE) from the first dose to 6 months post the final dose.
Detailed description
This study is a randomized, blinded study to evaluate the lot-to-lot consistency of immunogenicity, safety, and immune persistence of three consecutive manufacturing lots of EV71 vaccine, in children aged 6-35 months. The study is conducted to enroll 1500 healthy participants, including 600 infants aged 6-11 months, 600 toddlers aged 12-23 months, and 300 children aged 24-35 months. Eligibility will be assessed through medical history and physical examination. Participants from each age group will be randomly assigned to three different batch groups in a ratio of 1:1:1, that is, 500 participants in total will be in each lot arm, respectively. All participants will receive an injection of the EV71 vaccine in the anterolateral midthigh or deltoid muscle of the upper arm on Day 0 and Day 30, respectively. The duration of interventions for each participant is approximately 1 month, thus, the duration of the immune persistence study for each participant is approximately 25 months. For immunogenicity and immune persistence assessment, neutralizing antibodies against EV71 of all participants will be assessed on the first day (Day 0) before administration, 30 days after the final dose, and 12 and 24 months after the final dose, respectively. For safety assessment, observation of adverse events (AE) from Day 0 to Day 30 after each dose of vaccination will be evaluated by diary or contact cards. Simultaneously, the serious adverse event (SAE) between the first dose of the vaccine to 6 months after the final dose will be evaluated by diary or contact cards, active reports, investigators' phone calls, or on-site visits. Meanwhile, participants will be observed at clinical sites for at least 30 minutes.
Interventions
BIOLOGICALEV71 Vaccine
Inactivated enterovirus 71 vaccine (human diploid cell) of 3.0EU/0.5mL on Day 0,30
Sponsors
Centers for Disease Control and Prevention, China
Institute of Medical Biology, Chinese Academy of Medical Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
6 Months to 35 Months
Healthy volunteers
Yes
Inclusion criteria
* Age Requirement: Children aged 6 to 35 months at the time of enrollment. * Provision of legal Identification: Volunteers and their legal guardians or appointed representatives must provide valid legal identification documents. * Informed Consent: Legal guardians or appointed representatives of volunteers must have the capacity to understand the informed consent document and the research process, voluntarily participate, sign the informed consent form, and be able to comply with the study's requirements and complete relevant visits on time. * Temperature Requirement: Axillary body temperature prior to vaccination is less than 37.3°C.
Exclusion criteria
\[First Dose Exclusion Criterions\] Subjects meeting any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity index-geometric mean titer (GMT) of neutralizing antibody | Day 30 after the second vaccination | Neutralizing antibody assay will be performed using the neutralization and Microneutralization test method |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity index-geometric mean fold increase (GMFI) of neutralizing antibody | Between baseline and Day 30 after the second vaccination | Neutralizing antibody assay will be performed using the neutralization and Microneutralization test method |
| Immunogenicity index-seroconversion rates of neutralizing antibody | Between baseline and Day 30 after the second vaccination | Neutralizing antibody assay will be performed using the neutralization and Microneutralization test method. Seroconversion will be defined as a change from seronegative (\<1:8) to seropositive (≥1:8), or ≥4-fold increase from baseline |
| Immunogenicity index-seropositive rates of neutralizing antibody | Day 30, 12 months, and 24 months after the second vaccination | Neutralizing antibody assay will be performed using the neutralization and Microneutralization test method. Seropositive will be defined as the positive results with ties≥1:8 |
| Safety index-incidence of adverse reactions/events | 0-30 minutes after the first dose vaccination | Incidence of adverse reactions/events after the first dose vaccination |
| Safety index-incidence of serious adverse reactions/events | From the first dose to 6 months post the last dose of vaccination completed | Occurrence of serious adverse reactions/events after vaccination |
Countries
China
Contacts
Primary ContactWeijun Hu
Outcome results
None listed