Study of Japanese Encephalitis Chimeric Virus Vaccine Given With Measles-Mumps-Rubella Vaccine in Taiwanese Toddlers

Measles Clinical Trial

Official title:

Immunogenicity and Safety of Japanese Encephalitis Chimeric Virus Vaccine (JE CV) Concomitantly Administered With Measles, Mumps, and Rubella (MMR) Vaccine in Toddlers in Taiwan.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01188343
• Other study ID #: JEC04
• Secondary ID: UTN: U1111-1112-
• Status: Completed
• Phase: Phase 3
• First received: August 24, 2010
• Last updated: July 25, 2014
• Start date: August 2010
• Est. completion date: December 2012

Study information

• Verified date: July 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Interventional

Clinical Trial Summary

This study is designed to compare the immunogenicity of Japanese encephalitis chimeric virus vaccine (JE-CV) and measles-mumps-rubella (MMR)vaccine when given together or when given at separate visits 6 weeks apart in toddlers aged 12 to 18 months.

Primary objective:

• To demonstrate the non-inferiority of the antibody responses in terms of seroconversion of the concomitant administration of JE-CV and MMR compared to the antibody responses after the single administration of JE-CV and MMR vaccine.

Secondary objectives:

• To describe the immune response to JE CV and MMR before and after one dose of JE CV and MMR vaccine, respectively.

• To describe the safety of a single dose of JE-CV and MMR vaccine (given separately at a 6-week interval and the safety of the concomitant administration of JE-CV and MMR vaccine in all subjects up to 6 months after last vaccination.

Description:

All participants will receive Japanese encephalitis chimeric virus vaccine and measles-mumps-rubella vaccine and will be monitored for safety throughout the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 542
• Est. completion date: December 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 12 Months to 18 Months

Eligibility

Inclusion Criteria

• Aged 12 to 18 months on the day of inclusion .

• Born at full term of pregnancy (= 37 weeks) and with a birth weight = 2.5 kg.

• Subject in good health based on medical history and physical examination.

• Provision of informed consent form signed by at least one parent or other legally acceptable representative, and by an independent witness if the parents or legally acceptable representative cannot read.

• Subject and parent/legally acceptable representative or delegate able to attend all scheduled visits and comply with all trial procedures.

Exclusion Criteria

• Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination.

• Planned participation in another clinical trial during the present trial period.

• Receipt of any vaccine in the 4 weeks preceding the first trial vaccination except for pandemic influenza vaccination, which may be received at least two weeks before the study vaccines.

• Planned receipt of any vaccine up to the 6 weeks following the last trial vaccination except for pandemic influenza vaccine. In the event of a local or national immunization program with a pandemic influenza vaccine, participants who receive a pandemic influenza vaccine at any time during the trial will not be withdrawn from the trial.

• Previous vaccination against measles, measles-mumps-rubella (MMR), or flavivirus disease, including Japanese encephalitis (JE).

• Receipt of blood in the past 6 months that might interfere with the assessment of the immune response

• Receipt of intravenous injection of plasma, platelet product, or high dose of intravenous immunoglobulin in the past 11 months

• Receipt of intramuscular treatment of immunoglobulin or Hepatitis B immunoglobulin in the past 3 months

• Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term systemic corticosteroids therapy.

• Known history of human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C seropositivity.

• History of measles, mumps, rubella, or flavivirus infection confirmed either clinically, serologically, or microbiologically.

• Known systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to a vaccine containing any of the same substances .

• Known systemic hypersensitivity to gelatin, eggs, or anaphylactic/anaphylactoid reaction to neomycin.

• Known history of thrombocytopenia.

• Administration of any anti-viral within 2 months preceding first vaccination and up to the 6 weeks following the last trial vaccination.

• History of central nervous system disorder or disease, including seizures and febrile seizures.

• Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the Investigator.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

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

Intervention

Biological:
• Japanese encephalitis chimeric virus: Measles, mumps, and rubella live attenuated virus
0.5 mL each; Subcutaneous (SC)
• Japanese encephalitis chimeric virus: Measles, mumps, and rubella live attenuated virus
0.5 mL each, Subcutaneous (SC)
• Japanese encephalitis chimeric virus: Measles, mumps, and rubella live attenuated virus
0.5 mL each, subcutaneous (SC)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serological Status of Flavivirus at Before (Baseline) Concomitant Administration of JE-CV and MMR or Single Administration of JE-CV and MMR Vaccine	Neutralizing antibodies levels against dengue were only evaluated on subjects ELISA positive for Immunoglobulin G (IgG) or Immunoglobulin M (IgM). Flavivirus positive was defined as antibodies against JE-CV virus =10 (l/dil) or antibodies against at least one dengue virus serotype =10 (l/dil); Flavivirus negative was defined as antibodies against JE CV virus < 10 (l/dil) and antibodies against the 4 dengue virus serotypes < 10 (l/dil).	Day 0 (pre-vaccination)	No
Primary	Percentage of Participants With Seroconversion to Vaccine Antigens Following Concomitant Administration of Japanese Encephalitis Chimeric Virus Vaccine (JECV) and MMR or Single Administration of JE-CV and MMR Vaccine at 42 Days Following First Vaccination	JE-CV antigens were measured using a 50% plaque reduction neutralization test (PRNT50); MMR antigens were measured using enzyme linked immunosorbent assay (ELISA). Seroconversion was defined as: for JE-CV - participants with a pre-vaccination titer <1/10 and post-vaccination titer =1/10, or a pre-vaccination titer =1/10 and 4-fold increase from pre- to post; for Measles - post-vaccination titer =120 mIU/ml, when pre-vaccination titer is <120 mIU/ml; for Mumps - post-vaccination titer =1/10 U/ml when pre-vaccination titer is <10 U/ml; and for Rubella, post-vaccination titer =1/10 U/ml when pre-vaccination titer is <10 U/ml.	Day 0 (pre-vaccination) and Day 42 post-vaccination	No
Secondary	Percentage of Participants With Seroconversion to JE-CV and MMR Antigens Before and 42 Days Following Concomitant Administration of JE-CV and MMR or Single Administration of JE-CV and MMR Vaccine	JE-CV antigens were measured using a 50% plaque reduction neutralization test (PRNT50); MMR antigens were measured using enzyme linked immunosorbent assay (ELISA). Seroconversion was defined as: for JE-CV - participants with a pre-vaccination titer <1/10 and post-vaccination titer =1/10, or a pre-vaccination titer =1/10 and 4-fold increase from pre- to post; for Measles - post-vaccination titer =120 mIU/ml, when pre-vaccination titer is <120 mIU/ml; for Mumps - post-vaccination titer =1/10 U/ml when pre-vaccination titer is <10 U/ml; and for Rubella, post-vaccination titer =1/10 U/ml when pre-vaccination titer is <10 U/m	Pre-vaccination and Day 42 post-vaccination	No
Secondary	Number of Participants With Seroprotection to JE-CV and MMR Antigens Before, at Month 6 After Last Vaccination and Month 12 After First Following Concomitant Administration of JE-CV and MMR or Single Administration of JE-CV and MMR Vaccine	JE-CV antigens were measured using a 50% plaque reduction neutralization test (PRNT50); MMR antigens were measured using enzyme linked immunosorbent assay (ELISA). Seroprotection was defined as: for JE-CV - participants with a pre-vaccination titer <1/10 (1/dil) and post-vaccination titer =1/10, (1/dil) or a pre-vaccination titer =1/10 and 4-fold increase from pre- to post; for Measles - post-vaccination titer =120 mIU/ml, when pre-vaccination titer is <120 mIU/ml; for Mumps - post-vaccination titer =1/10 units/ml when pre-vaccination titer is <10 units/ml; and for Rubella, post-vaccination titer =1/10 IU/ml when pre-vaccination titer is <10 IU/m	Pre-vaccination and up to Month 12 post-vaccination	No
Secondary	Geometric Mean Titers of Antibodies to Vaccine Antigens Before and After Concomitant Administration of JE-CV and MMR or Single Administration of JE-CV and MMR Vaccine	JE-CV antigens were measured using a 50% plaque reduction neutralization test (PRNT50); MMR antigens were measured using enzyme linked immunosorbent assay (ELISA).	Pre-vaccination and Day 42 post-vaccination	No
Secondary	Number of Participants Reporting Solicited Injection Site and Systemic Reactions Following Administration of JE-CV Vaccine	Solicited injection site: Pain, Erythema, and Swelling; Solicited systemic reactions: Fever (Temperature), Vomiting, Crying Abnormal, Drowsiness, Appetite Lost, and Irritability. Grade 3 injection site: Pain - Cries when injected limb is moved or movement of limb is reduced; Erythema and Swelling - =5 cm. Grade 3 systemic reactions: Fever - >39.5°C; Vomiting - =6 episodes per 24 hours or requiring parenteral hydration; Crying Abnormal - >3 hours; Drowsiness - Sleeping most of the time or difficult to wake; Appetite Lost - Refused =3 feeds/meals or refused most feeds/meals; Irritability - Inconsolable.	Day 0 up to Day14 post-vaccination	No
Secondary	Number of Participants Reporting Solicited Injection Site and Systemic Reactions Following Administration of MMR Vaccine	Solicited injection site: Pain, Erythema, and Swelling; Solicited systemic reactions: Fever (Temperature), Vomiting, Crying Abnormal, Drowsiness, Appetite Lost, and Irritability. Grade 3 injection site: Pain - Cries when injected limb is moved or movement of limb is reduced; Erythema and Swelling - =5 cm. Grade 3 systemic reactions: Fever - >39.5°C; Vomiting - =6 episodes per 24 hours or requiring parenteral hydration; Crying Abnormal - >3 hours; Drowsiness - Sleeping most of the time or difficult to wake; Appetite Lost - Refused =3 feeds/meals or refused most feeds/meals; Irritability - Inconsolable.	Day 0 up to Day 14 post-vaccination	No

External Links

•   Link
•   Link