This study is a randomized, double-blinded, placebo-controlled phase 2 clinical trial to evaluate the immunogenicity and safety of Inactivated Rotavirus Vaccine (IRV) in children (aged 2-71 months). Primary immunogenicity endpoints in two age groups are the anti-RV neutralizing antibody geometric mean titers (GMTs) 28 days after the final dose, anti-RV neutralizing antibody geometric mean increase (GMI), and seroconversion rates between baseline and 28 days after the final dose. The secondary 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 28/30 days after each dose, and the number of serious adverse events (SAE) between the first dose up to 6 months after the final dose. The exploratory endpoints are the anti-RV IgG and IgA antibody GMT 28 days after the final dose, GMI and seroconversion rates of anti-RV IgG and IgA antibody between baseline and 28 days after the final dose, GMT and seropositive rates of anti-RV neutralizing antibody, IgG antibody and IgA antibody 90, 180, and 360 days after the final dose. Besides, as the exploratory endpoint, the GMT, GMI, and seroconversion rates of cross-neutralizing antibodies against G3 and G9 type of RV, gene transcription differences in peripheral blood mononuclear cells on Day 0 and 28 after the final dose will be assessed.
This is a randomized, double-blinded, placebo-controlled phase 2 clinical trial to evaluate immunogenicity and safety of IRV performed in 600 subjects (aged 2-71 months). Then, 300 toddlers (aged 7-71 months) and 300 infants (aged 2-6 months) will be eligible for parallel enrollment after assessing through medical history and physical examination. Subjects from each age group will be randomly assigned to the vaccine group or placebo group in a ratio of 3:1, that is, 225 subjects of all age groups will be injected with the vaccine while 75 subjects with the placebo. Toddlers (aged 7-71 months) will receive an injection of the vaccine or placebo in the anterolateral midthigh or deltoid muscle of the upper arm on Day 0 and 28. Infants (aged 2-6 months) will receive an injection of the vaccine or placebo in the anterolateral midthigh or deltoid muscle of the upper arm on Day 0, 28, and 56. There would be 140 subjects in each age group chosen voluntarily for the immune persistence cohort according to the order of enrollment. The duration of toddlers (aged 7-71 months) for intervention is approximately 1 month. Thus, the duration of each subject enrolled in the immune persistence cohort will be approximately 13 months while the duration of the rest of the subjects in the study will be approximately 7 months. The duration of infants (aged 2-6 months) for intervention is approximately 2 months. Thus, the duration of each subject enrolled in the immune persistence cohort will be approximately 14 months while the duration of the rest of the subjects in the study will be approximately 8 months. For safety assessment, the observation and evaluation of adverse events (AE) from Day 0 to Days 28/30 after each dose, and serious adverse events (SAE) between the first dose up to 6 months after the final dose will be evaluated by diary/contact cards, active reports by subjects' legal guardians, or investigators' phone calls as well as face-to-face visits. Meanwhile, subjects will be observed at the site for at least 30 minutes after each dose. For immunogenicity assessment, neutralizing antibodies against the strain from which the vaccine is based (homologous ZTR-68 strain (G1P\[8\]), IgG antibodies, IgA antibodies of all subjects, and neutralizing antibodies against the G3 and G9 type RV in 140 subjects of each age group will be assessed. For the exploratory endpoint, the gene transcription level of PBMC will be examined for the preliminary exploration of the possible mechanism of the Inactivated Rotavirus Vaccine (Vero Cells).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
600
Inactivated Rotavirus vaccine (Vero Cells) of 320EU/0.5ml on Day 0, 28
Inactivated Rotavirus vaccine (Vero cell) of 320EU/0.5ml on Day 0, 28, 56
Two doses of placebo at the vaccination schedule of Day 0, 28
Three doses of placebo at the vaccination schedule of Day 0, 28, 56
Tongxu Center for Disease Prevention and Control
Kaifeng, Henan, China
RECRUITINGImmunogenicity index-geometric mean titer (GMT) of neutralizing antibody
Neutralizing antibody assay will be performed using the neutralization and ELISA method.
Time frame: Day 28 after the second vaccination
Immunogenicity index-geometric mean titer (GMT) of neutralizing antibody
Neutralizing antibody assay will be performed using the neutralization and ELISA method.
Time frame: Day 28 after the third vaccination
Immunogenicity index-geometric mean increase (GMI) of neutralizing antibody
Neutralizing antibody assay will be performed using the neutralization and ELISA method.
Time frame: Between baseline and day 28 after the second vaccination
Immunogenicity index-geometric mean increase (GMI) of neutralizing antibody
Neutralizing antibody assay will be performed using the neutralization and ELISA method.
Time frame: Between baseline and day 28 after the third vaccination
Immunogenicity index-seroconversion rates of neutralizing antibody
Neutralizing antibody assay will be performed using the neutralization and ELISA method. Seroconversion will be defined as a change from seronegative (\<1:8) to seropositive (≥1:8), or a ≥4-fold increase from baseline.
Time frame: Between baseline and day 28 after the second vaccination
Immunogenicity index-seroconversion rates of neutralizing antibody
Neutralizing antibody assay will be performed using the neutralization and ELISA method. Seroconversion will be defined as a change from seronegative (\<1:8) to seropositive (≥1:8), or a ≥4-fold increase from baseline.
Time frame: Between baseline and day 28 after the third vaccination
Safety index-incidence of adverse reactions/events
Incidence of adverse reactions/events after the first dose vaccination.
Time frame: 0-30 minutes after the first dose vaccination
Safety index-incidence of adverse reactions/events
Incidence of adverse reactions/events after the second dose vaccination.
Time frame: 0-30 minutes after the second dose vaccination
Safety index-incidence of adverse reactions/events
Incidence of adverse reactions/events after the third dose vaccination.
Time frame: 0-30 minutes after the third dose vaccination
Safety index-incidence of solicited adverse reactions/events
Incidence of solicited adverse reactions/events after the first dose vaccination.
Time frame: Day 0 to 7 after the first dose vaccination
Safety index-incidence of solicited adverse reactions/events
Incidence of solicited adverse reactions/events after the second dose vaccination.
Time frame: Day 0 to 7 after the second dose vaccination
Safety index-incidence of solicited adverse reactions/events
Incidence of solicited adverse reactions/events after the third dose vaccination.
Time frame: Day 0 to 7 after the third dose vaccination
Safety index-incidence of unsolicited adverse reactions/events
Incidence of unsolicited adverse reactions/events after the first dose vaccination.
Time frame: Day 0 to 28 after the first dose vaccination
Safety index-incidence of unsolicited adverse reactions/events
Incidence of unsolicited adverse reactions/events after the second dose vaccination.
Time frame: Day 0 to 28/30 after the second dose vaccination
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Safety index-incidence of unsolicited adverse reactions/events
Incidence of unsolicited adverse reactions/events after the third dose vaccination.
Time frame: Day 0 to 30 after the third dose vaccination
Safety index-incidence of serious adverse events
Occurrence of serious adverse reactions/events after vaccination.
Time frame: From the beginning of the vaccination up to 6 months after the last vaccination completed