Immunogenicity of Japanese Encephalitis Vaccine Co-administered With Measles-Mumps-Rubella Vaccine (MMR)

Measles Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06331702
• Other study ID #: CDBJEIV2023001
• Status: Recruiting
• Phase: Phase 4
• Start date: March 2, 2024
• Est. completion date: December 31, 2024

Study information

• Verified date: March 2024
• Source: Liaoning Chengda Biotechnology CO., LTD
• Contact: Li Tong
• Phone: +86 15811315908
• Email: 14877107[@]qq.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 396
• Est. completion date: December 31, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Months to 12 Months

Eligibility

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)

• Receipt of immunosuppressive therapy within 3 months prior to enrollment, such as cytotoxic therapy, steroid therapy (defined as continuous oral or intravenous infusion for more than 14 days, with a glucocorticoid dose of =0.5 mg/kg/day, unrestricted for inhaled and local steroids), or long-term other immunomodulatory drugs.

• Serious illness (acute or chronic), known or suspected, such as complicated diabetes, infectious, purulent, and allergic skin diseases, Down's syndrome, sickle cell anemia, cardiovascular and cerebrovascular diseases, liver and kidney diseases, respiratory diseases, malignant tumors, etc.

• Contraindications to intramuscular injection, such as diagnosed with thrombocytopenia, any coagulation disorders, or receiving anticoagulant treatment.

• History of convulsions, epilepsy, encephalopathy, mental illness or other neurological disorders, or a family history of mental illness.

• Plans to move out of the local area before the end of the experiment or leave the local area for a long time during the scheduled trial visit period.

• Any conditions that may interfere with the evaluation of the experimental purpose, as deemed by the researcher.

Related Conditions & MeSH terms

• Encephalitis
• Encephalitis, Japanese
• Japanese Encephalitis
• Measles
• Mumps
• Rubella

Intervention

Biological:
• Vero cell-drived inactive Japanese encephalitis vaccine
0.5ml for each dose, manufactured by Liaoning Chengda Biotechnology CO., LTD, administered in the deltoid area of lateral arm by intramuscular injection.
• Measles-Mumps-Rubella Vaccine
0.5ml for each dose (after dissolving), manufactured by Shanghai Institute of Biological Products CO., LTD, administered in the lower part of the deltoid area of lateral arm, by subcutaneous injection.

Locations

Country	Name	City	State
China	Jiangsu Provincial Center for Disease Control and Prevention	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Liaoning Chengda Biotechnology CO., LTD

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Antibody Titer for Post 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).	30 days after the last dose of vaccination
Primary	Seroconversion Rate for Post 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.	30 days after the last dose of vaccination
Secondary	Incidence of Any Local and Systemic Adverse Events Within 30 Minutes of Each Vaccination	Participants will be observed at the clinical site for 30 minutes after each dose of vaccine. Any adverse events at the vaccination site (local) and non vaccination site (systemic) are collected. Adverse Events (AEs) are defined as all adverse medical events that occur in participants after receiving the investigational drug, which can manifest as symptoms, signs, diseases, or abnormal laboratory tests, but may not necessarily have a causal relationship with the investigational drug.	30 minutes following each vaccination
Secondary	Incidence of Solicited Local and Systemic Adverse Events Within 7 Days of Each Vaccination	Parents use a structured diary card to record the following solicited (pre-listed) local and system reactions from 30 minutes through 7 days following vaccination: Local reactions: Induration; Swelling; Rash; Tenderness; Systemic reactions: Fever; Diarrhea; Constipation; Dysphagia; Anorexia; Sickness; Vomiting; Syncope; Convulsions; Cough; Pruritus; Irritability or Sleepiness; Skin and mucosal abnormalities; Fatigue; Acute Allergic Reactions	30 minutes through 7 days following each vaccination
Secondary	Incidence of Unsolicited Adverse Events and Serious Adverse Events Within 30 Days of Post Vaccination	Unsolicited adverse events and serious adverse events within 30 days of post vaccination will be collected through a combination of telephone visits by researchers and active reporting by participants.; Serious adverse events are those meeting one of the following conditions: Death; Life threatening; Resulted in a persistent or significant disability or incapacity; Required inpatient hospitalization or prolongation of existing hospitalization.; Congenital abnormalities or birth defects.	30 days of post vaccination