Rotavirus Infection
Conditions
Brief summary
This study is a randomized, double-blinded, placebo-controlled, Phase 1, dose-escalation study to evaluate the safety, reactogenicity and immunogenicity of Inactivated Rotavirus Vaccine (IRV) performed in healthy adult (aged 18-49 years), adolescent (aged 6-17 years) and infant subjects (aged 2-71 months). Primary objectives of the clinical trial include assessing the safety and tolerability of IRV given at two and three dose levels and comparing the safety and tolerability of IRV after each vaccination, between dosage groups, and by pre-vaccination rotavirus immune status. Secondary objective of the clinical trial is immunogenicity evaluation after each vaccination, between dosage groups, and by pre-vaccination rotavirus immune status.
Detailed description
This clinical trial aimed to evaluate safety and immunogenicity effect of IRV（Vero cell）in Chinese healthy adults, adolescents and infants. The subjects were divided into 5 groups. Two dose and three dose levels will be evaluated. Adult (aged 18-49 years), adolescents (aged 6-17 years), infant subjects (aged 7-71 months) and infant subjects (aged 2-6 months) will receive intramuscular (IM) injection on Days 0 and 28. Infant subjects (aged 2-6 months) subjects will receive intramuscular (IM) injection on Days 0 , 28 and 56. Three dose subgroups (low dose, medium dose and high dose were included in each age group. To maintain blindness in the trial, subjects were randomized in a 3:1 ratio to receive different dosages of the vaccine group or placebo group. In the analysis, the placebo subjects of the same age group were combined to ensure that the analysis ratio of the experimental vaccine group to the placebo group is 1:1. Therefore, 24 subjects in the experimental vaccine group and 8 subjects in the placebo group were chose in each dose group. Subjects were randomized to receive different dosages of the vaccine or placebo. Vaccination was performed in the adult group first, then on the adolescents, and on the infants last. Within each age group, dose-escalation with the principle from low to high dosage.
Interventions
BIOLOGICALLow dosage IRV on a 0- and 28-day schedule
Inactivated Rotavirus vaccine (Vero cell) of 80EU/0.5ml on day 0, 28
BIOLOGICALMedium dosage IRV on a 0- and 28-day schedule
Inactivated Rotavirus vaccine (Vero cell) of 160EU/0.5ml on day 0, 28
BIOLOGICALHigh dosage IRV on a 0- and 28-day schedule
Inactivated Rotavirus vaccine (Vero cell) of 320EU/0.5ml on day 0,28
BIOLOGICALLow dosage IRV on a 0- , 28- and 56-day schedule
Inactivated Rotavirus vaccine (Vero cell) of 80EU/0.5ml on day 0,28,56
BIOLOGICALMedium dosage IRV on a 0- , 28- and 56-day schedule
Inactivated Rotavirus vaccine (Vero cell) of 160EU/0.5ml on day 0,28,56
BIOLOGICALHigh dosage IRV on a 0- , 28- and 56-day schedule
Inactivated Rotavirus vaccine (Vero cell) of 320EU/0.5ml on day 0,28,56
BIOLOGICALPlacebo on day 0, 28
Two doses of placebo at the vaccination schedule of day 0,28
BIOLOGICALPlacebo on day 0, 28, 56
Three doses of placebo at the vaccination schedule of day 0, 28,56
Sponsors
Henan Provincal Center for Disease Control and Prevention
Chinese Academy of Medical Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Months to 49 Years
Healthy volunteers
Yes
Inclusion criteria
1. 2 months old to 49 years old, healthy resident, excluding the following: * Congenital malformations, developmental disorders, genetic defects, severe malnutrition and other conditions； * Have Congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia, systemic lupus Erythematosus (SLE) , juvenile Rheumatoid Arthritis, or other autoimmune diseases； * History of Cerebral Palsy, seizures, mental illness. 2. I and/or my guardian voluntarily participate and sign an informed consent form, and can follow the requirements of the clinical trial protocol; 3. Have never received oral rotavirus live attenuated vaccine.
Exclusion criteria
* First dose
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety index-incidence of abnormal blood routine assessment | Day 4 after the first dose vaccination | Incidence of abnormal blood routine assessment at Day 4 after the first dose vaccination, except children aged Month 2-71 |
| Safety index-incidence of serious adverse events | From the beginning of the vaccination to 6 months after the last vaccination completed | Occurrence of serious adverse reactions/events after vaccination. |
| Safety index-incidence of abnormal urine routine assessment | Day 4 after the first dose vaccination | Incidence of abnormal urine routine assessment at Day 4 after the first dose vaccination, except children aged Month 2-71 |
| Safety index-incidence of abnormal blood biochemistry assessment | Day 4 after the first dose vaccination | Incidence of abnormal blood biochemistry assessment at Day 4 after the first dose vaccination, except children aged Month 2-71 |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity index-seroconversion rates of neutralizing antibody | Day 28 after the second dose vaccination | 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 ≥4-fold increase from baseline. |
| Immunogenicity index-geometric mean titer (GMT) of neutralizing antibody | Day 28, 90, 180 after the second dose vaccination | Neutralizing antibody assay will be performed using the neutralization and ELISA method. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity index-geometric mean titer (GMT) of IgA antibody | Day 28, 90, 180 after the second dose vaccination | IgA antibody assay will be performed using the ELISA method. |
| Cellular immune responses of cytokines | Day 14 after the second vaccination | Cytokines (IL-2, IL-4, IL-6, IL-10, TNF - α and IFN - γ) responses of children aged 7-71 months will be measured using ELISA method. |
| Cellular immune responses of lymphocytes | Day 14 after the second vaccination | Lymphocytes (NK cells, B lymphocytes and T lymphocyte) responses of children aged 7-71 months will be measured using Flow cytometry. |
| Immunogenicity index-geometric mean titer (GMT) of IgG antibody | Day 28, 90, 180 after the second dose vaccination | IgG antibody assay will be performed using the ELISA method. |
| Immunogenicity index-seroconversion rates of IgG antibody | Day 28 after the second dose vaccination | IgG antibody assay will be performed using the ELISA method. Seroconversion will be defined as a change from seronegative (\<1:8) to seropositive (≥1:8), or ≥4-fold increase from baseline. |
| Immunogenicity index-seroconversion rates of IgA antibody | Day 28 after the second vaccination | IgA antibody assay will be performed using the ELISA method. Seroconversion will be defined as a change from seronegative (\<1:8) to seropositive (≥1:8), or ≥4-fold increase from baseline. |
Countries
China
Outcome results
None listed