Immunogenicity and Safety of ChimeriVax™ Japanese Encephalitis Vaccine in Thai Toddlers and Children

Phase 2

Completed

• Conditions: Japanese Encephalitis; Hepatitis A
• Interventions: Biological: Hepatitis A vaccine (Day 0) Japanese encephalitis vaccine (Day 28); Biological: Japanese encephalitis vaccine (Day 0) Hepatitis A vaccine (Day 28)

• Registration Number: NCT00621764
• Lead Sponsor: Sanofi Pasteur, a Sanofi Company

Brief Summary

Safety:

To describe the safety profiles following vaccination.

Immunogenicity:

To describe the immune response after a single dose of vaccine.

Detailed Description

This is a randomized, cross-over, open, active controlled, multi-center trial in toddlers and children in Thailand. Stepwise enrollment of children in 2 age cohorts. Subjects will be followed for 5 years.

Study Timeline

• Study First Submitted: 2008-02-12
• Study First Submitted QC: 2008-02-21
• Study First Posted: 2008-02-22
• Study Start: 2008-03
• Primary Completion: 2009-12
• Study Completion: 2013-05
• Status Verified: 2014-09
• Results First Submitted: 2014-09-09
• Results First Submitted QC: 2014-09-22
• Last Update Submitted: 2014-09-23
• Results First Posted: 2014-09-25
• Last Update Posted: 2014-10-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• Provision of consent form signed by at least one parent or another legally acceptable representative, and by at least one independent witness.
• Completion of vaccinations according to the national immunization schedule
• Subject and parent/legally acceptable representative able to attend all scheduled visits and comply with all trial procedures.
• Previous receipt of two doses of a mouse-brain-derived JE vaccine at 12 to 15 months of age according to the national immunization schedule and aged 2 to 5 years on the day of inclusion.
• Aged 12 to 24 months on the day of inclusion and have not received any JE vaccine.

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.
• 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 systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to the trial vaccine or to a vaccine containing any of the same substances.
• Chronic illness, at a stage that could interfere with trial conduct or completion, in the opinion of the Investigator.
• Receipt of blood or blood-derived products in the past 3 months, that might interfere with the assessment of the immune response.
• Receipt of hepatitis A vaccine.
• History of flavivirus infection (confirmed either clinically, serologically or microbiologically).
• Administration of any anti-viral within 2 months preceding the screening visit.
• History of central nervous system disorder or disease.
• Personal or family history of thymic pathology (thymoma), thymectomy, or myasthenia.
• Planned participation in another clinical trial during the present trial period.
• Receipt of any vaccine in the 4 weeks preceding the first trial vaccination.
• Planned receipt of any vaccine in the 4 weeks following any trial vaccination.
• Personal human immunodeficiency virus, hepatitis B or hepatitis C seropositivity in the blood sample taken at screening.
• Thrombocytopenia, bleeding disorder or anticoagulants in the 3 weeks preceding inclusion contraindicating IM vaccination.
• Previous vaccination against flavivirus disease at any time before the trial other than a mouse-brain-derived JE vaccine given in a two-dose regimen at 12 to 15 months of age in accordance with the national immunization schedule.
• Febrile illness or any acute illness/infection on the day of vaccination, according to investigator judgment
• History of seizures.
• Previous vaccination against flavivirus disease.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Hepatitis A/JE-CV (Group 2)	Hepatitis A vaccine (Day 0) Japanese encephalitis vaccine (Day 28)	Participants aged 2 to 5 years at enrollment; to receive Hepatitis A vaccine (Day 0) and Japanese encephalitis vaccine (Day 28)
Hepatitis A/JE-CV (Group 4)	Hepatitis A vaccine (Day 0) Japanese encephalitis vaccine (Day 28)	Participants aged 12 to 24 months at enrollment; to receive Hepatitis A vaccine (Day 0) and Japanese encephalitis vaccine (Day 28)
JE-CV/Hepatitis A (Group 1)	Japanese encephalitis vaccine (Day 0) Hepatitis A vaccine (Day 28)	Participants aged 2 to 5 years at enrollment; to receive Japanese encephalitis vaccine (Day 0) and Hepatitis A vaccine (Day 28)
JE-CV/Hepatitis A (Group 3)	Japanese encephalitis vaccine (Day 0) Hepatitis A vaccine (Day 28)	Participants aged 12 to 24 months at enrollment; to receive Japanese encephalitis vaccine (Day 0) and Hepatitis A vaccine (Day 28)

Primary Outcome Measures

Name	Time	Method
Number of Participants With Solicited Injection Site and Systemic Reactions After Injection With Either JE-CV or Hepatitis A Vaccine as First Injection	Day 0 up to Day 14 post-vaccination	12 to 24 months - Injection site: Tenderness, Erythema, and Swelling; Systemic reactions: Fever, Vomiting, Crying Abnormal, Drowsiness, Appetite lost, and Irritability. Grade 3: Tenderness, Cries if limb is moved; Erythema and Swelling, ≥5 cm; Fever, \>39.5˚C; Vomiting, ≥ 6 times/day; Abnormal crying, \>3 hours; Drowsiness, Sleeping often; Appetite lost, Refuses ≥3 feeds/meals; Irritability, Inconsolable.; 2 to 5 years - Injection site: Pain, Erythema, and Swelling; Systemic reactions: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3: Pain, Incapacitating; Erythema and Swelling, ≥5 cm; Fever, \>39˚C; Headache, Malaise, and Myalgia, Prevents activities.
Number of Participants With Solicited Injection Site and Systemic Reactions After Injection With Either JE-CV or Hepatitis A Vaccine as Second Injection	Day 0 up to Day 14 post-vaccination	12 to 24 months - Injection site: Tenderness, Erythema, and Swelling; Systemic reactions: Fever, Vomiting, Crying Abnormal, Drowsiness, Appetite lost, and Irritability. Grade 3: Tenderness, Cries if limb is moved; Erythema and Swelling, ≥5 cm; Fever, \>39.5˚C; Vomiting, ≥ 6 times/day; Abnormal crying, \>3 hours; Drowsiness, Sleeping often; Appetite lost, Refuses ≥3 feeds/meals; Irritability, Inconsolable.; 2 to 5 years - Injection site: Pain, Erythema, and Swelling; Systemic reactions: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3: Pain, Incapacitating; Erythema and Swelling, ≥5 cm; Fever, \>39˚C; Headache, Malaise, and Myalgia, Prevents activities.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Seroconversion to JE-CV Vaccine Antigens Following Administration of JE-CV Vaccination	Day 0 (pre-vaccination) and Day 28 after final vaccination	JE virus neutralizing antibody measurement was assessed by plaque reduction neutralization test (PRNT50). Seroconversion was defined as participants with a pre-vaccination titer \< 10 (1/dil) and post-vaccination titer ≥ 10 (1/dil), or participants with pre-vaccination titer ≥ 10 (1/dil) and 4-fold increase from pre- to post-vaccination.
Summary of Geometric Mean Titers Against JE Antibodies Before and After JE-CV Vaccination	Day 0 (pre-vaccination) and Day 28 after final vaccination	JE virus neutralizing antibody measurement was assessed by the PRNT50 assay.