A Phase Ⅳ, Randomized, Controlled, Open-label, Immunogenicity Study of Vero Cell-derived Inactivated Japanese Encephalitis Vaccine (JEV-I) Co-administered With Measles-Mumps-Rubella Vaccine (MMR)
Overview
- Phase
- Phase 4
- Intervention
- Vero cell-drived inactive Japanese encephalitis vaccine
- Conditions
- Japanese Encephalitis
- Sponsor
- Liaoning Chengda Biotechnology CO., LTD
- Enrollment
- 408
- Locations
- 1
- Primary Endpoint
- Antibody Titer for Post Vaccination
- Status
- Completed
- Last Updated
- 8 months ago
Overview
Brief Summary
This is a phase IV, randomized, controlled, open-label study proceed in healthy children aged 8 months in China. The primary objective is to demonstrate the immunogenicity of simultaneous administration of JEV-I and MMR is not inferior to that of separate administration, as measured by seroconversion rates and antibody titers against the four antigens. The secondary objective is to describe the safety of the vaccines when administered simultaneously or separately.
Detailed Description
According to current immunization programs in China, there is an overlap in the vaccination schedules for JEV-I and MMR. Children are recommended to receive 2 doses of JEV-I at 8 months of age, with an interval of 7-10 days. The MMR vaccine is also recommended for administration at 8 months of age. Administering JEV-I and MMR vaccines simultaneously at 8 months of age may facilitate adherence to vaccination programs, reduce the burden of medical treatment for parents and children who receive both vaccines separately, and improve the efficiency of vaccination work. This is a phase IV, randomized, controlled, open-label study proceed in healthy children aged 8 months in China. The primary objective is to demonstrate the immunogenicity of simultaneous administration of JEV-I and MMR is not inferior to that of separate administration, as measured by seroconversion rates and antibody titers against the four antigens. The secondary objective is to describe the safety of the vaccines when administered simultaneously or separately. The children aged 8 months who have not received any Japanese encephalitis vaccine or MMR (or vaccines containing related ingredients) will be recruited and randomly assigned to one of three study groups (1:1:1 ratio): Group 1, Group 2 and Group 3. Participants in Group 1 will receive JEV-I (dose 1) and MMR simultaneously for the first time. Participants in Group 2 will receive JEV-I only. Participants in Group 3 will receive MMR only. Blood will be collected pre-vaccination (Day 0) and 30 days post vaccination to evaluate seroconversion rates and antibody titers against the four antigens. After each vaccination, all participants will be observed at the clinical site for at least 30 minutes for immediate reactions and will be monitored for solicited adverse events (AEs) for 7 days post vaccination. All participants will be monitored for unsolicited AEs and serious adverse events within 30 days of post vaccination.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants aged 8 months to \<12 months at the time of enrollment
- •Participants are able to provide valid identification documents of themselves and/or their legal guardian (entrusted person).
- •Legal guardian of the participants can understand requirements and processes of the study, voluntarily agree to participate in the clinical trial, provide informed consent, accept all scheduled visits.
Exclusion Criteria
- •Axillary temperature \>37.0 ℃ at the time of enrollment.
- •Participating in another clinical trial or planning to participate in another clinical trial during the course of this trial.
- •Previous receipt of the Japanese encephalitis vaccine or the measles-mumps-rubella vaccine (or a vaccine containing any of these components), or plan to receive other vaccines of the same type or composition during the trial period.
- •History of measles, mumps, rubella, or Japanese encephalitis infection (confirmed by clinical, serological, or microbiological methods).
- •Received blood or blood products within 3 months before enrollment.
- •History of allergies to any component of the experimental vaccine, or severe allergies to other vaccine or drugs administered in the past, such as anaphylactic shock, laryngeal edema, henoch-schonlein purpura, thrombocytopenic purpura, arthur reaction, dyspnea, angioneuroedema, systemic rash and/or urticaria.
- •History of attenuated live vaccine administration within 14 days prior to vaccination, or history of other non live vaccine administration within 7 days prior to vaccination.
- •Acute febrile diseases (axillary body temperature ≥ 38.5 ℃) or in acute stage of chronic diseases, or taking antipyretics, analgesics, and anti-allergic agents within 3 days before vaccination.
- •Primary or acquired immunodeficiency, such as human immunodeficiency virus infection (participants themselves or their mothers are infected with human immunodeficiency virus), systemic lupus erythematosus, guillain-barre syndrome, or other autoimmune diseases.
- •Primary or acquired immune dysfunction (history of thyroid, pancreatic, liver, and spleen resection)
Arms & Interventions
Group 1 (JEV-I and MMR co-administration group)
Participants will receive 1 dose of JEV-I and 1 dose of MMR concurrently on Day 0, with each vaccine administered on a different side of the body, and a second dose of JEV-I 7-10 days later. Blood sampling will be performed on Day 0 and 30 days after the second dose of JEV-I.
Intervention: Vero cell-drived inactive Japanese encephalitis vaccine
Group 1 (JEV-I and MMR co-administration group)
Participants will receive 1 dose of JEV-I and 1 dose of MMR concurrently on Day 0, with each vaccine administered on a different side of the body, and a second dose of JEV-I 7-10 days later. Blood sampling will be performed on Day 0 and 30 days after the second dose of JEV-I.
Intervention: Measles-Mumps-Rubella Vaccine
Group 2 (JEV-I administered separately)
Participants will receive 2 doses of JEV-I (7-10 days apart). Blood sampling will be performed on Day 0 and 30 days after the second dose of JEV-I.
Intervention: Vero cell-drived inactive Japanese encephalitis vaccine
Group 3 (MMR administered separately)
Participants will receive 1 doses of MMR. Blood sampling will be performed on Day 0 and Day 30.
Intervention: Measles-Mumps-Rubella Vaccine
Outcomes
Primary Outcomes
Antibody Titer for Post Vaccination
Time Frame: 30 days after the last dose of vaccination
The serum neutralizing antibody titer against Japanese encephalitis virus is measured by plaque reduction neutralization test (PRNT). The immunoglobulin (IgG) antibody titers against measles virus, mumps virus, and rubella virus are measured using enzyme-linked immunosorbent assay (ELISA).
Seroconversion Rate for Post Vaccination
Time Frame: 30 days after the last dose of vaccination
The seroconversion rate for JEV-I post vaccination is defined as the percentage of participants with a change in serum anti-JE neutralizing antibody from PRNT titer \<1:10 at baseline to titer ≥1:10 30 days after the last dose of vaccination or a 4-fold rise from baseline. The seroconversion rate for MMR post vaccination is defined as the percentage of participants with a change in serum measles IgG antibody from titer \<200 milli international units (mIU)/mL at baseline to titer ≥200 mIU/mL post vaccination or a 4-fold rise from baseline, and serum mumps IgG antibody from titer \<100 international units (IU)/mL to titer ≥100 IU/mL or a 4-fold rise from baseline, and serum rubella IgG antibody from titer \<20 IU/mL to titer ≥20 IU/mL or a 4-fold rise from baseline, as measured by ELISA.
Secondary Outcomes
- Incidence of Any Local and Systemic Adverse Events Within 30 Minutes of Each Vaccination(30 minutes following each vaccination)
- Incidence of Solicited Local and Systemic Adverse Events Within 7 Days of Each Vaccination(30 minutes through 7 days following each vaccination)
- Incidence of Unsolicited Adverse Events and Serious Adverse Events Within 30 Days of Post Vaccination(30 days of post vaccination)