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

A Controlled Study of the Safety and Immunogenicity of ChimeriVax™ Japanese Encephalitis Vaccine in Thai Toddlers and Children

Safety:

To describe the safety profiles following vaccination.

Immunogenicity:

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

Study Overview

• Status: Completed
• Conditions: Japanese Encephalitis; Hepatitis A
• Intervention / Treatment: Biological: Japanese encephalitis vaccine (Day 0) Hepatitis A vaccine (Day 28); Biological: Japanese encephalitis vaccine (Day 0) Hepatitis A vaccine (Day 28); Biological: Hepatitis A vaccine (Day 0) Japanese encephalitis vaccine (Day 28)

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 Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 2

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10400
  • Bangkok, Thailand, 10700
  • Bangkok, Thailand, 10330

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 5 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JE-CV/Hepatitis A (Group 1); Participants aged 2 to 5 years at enrollment; to receive Japanese encephalitis vaccine (Day 0) and Hepatitis A vaccine (Day 28)	Biological: Japanese encephalitis vaccine (Day 0) Hepatitis A vaccine (Day 28); ≥4.0 Log10 Plaque forming units (PFU), Subcutaneous (SC; Day 0); 0.5 mL intramuscular (IM; Day 28); Other Names: ChimeriVax™-JE; Biological: Japanese encephalitis vaccine (Day 0) Hepatitis A vaccine (Day 28); ≥4.0 Log10 PFU SC (Day 0); 0.5 mL IM (Day 28); Other Names: ChimeriVax™-JE
Experimental: Hepatitis A/JE-CV (Group 2); Participants aged 2 to 5 years at enrollment; to receive Hepatitis A vaccine (Day 0) and Japanese encephalitis vaccine (Day 28)	Biological: Hepatitis A vaccine (Day 0) Japanese encephalitis vaccine (Day 28); 0.5 mL IM (Day 0); ≥4.0 Log10 PFU SC (Day 28); Other Names: ChimeriVax™-JE
Experimental: JE-CV/Hepatitis A (Group 3); Participants aged 12 to 24 months at enrollment; to receive Japanese encephalitis vaccine (Day 0) and Hepatitis A vaccine (Day 28)	Biological: Japanese encephalitis vaccine (Day 0) Hepatitis A vaccine (Day 28); ≥4.0 Log10 Plaque forming units (PFU), Subcutaneous (SC; Day 0); 0.5 mL intramuscular (IM; Day 28); Other Names: ChimeriVax™-JE; Biological: Japanese encephalitis vaccine (Day 0) Hepatitis A vaccine (Day 28); ≥4.0 Log10 PFU SC (Day 0); 0.5 mL IM (Day 28); Other Names: ChimeriVax™-JE
Experimental: Hepatitis A/JE-CV (Group 4); Participants aged 12 to 24 months at enrollment; to receive Hepatitis A vaccine (Day 0) and Japanese encephalitis vaccine (Day 28)	Biological: Hepatitis A vaccine (Day 0) Japanese encephalitis vaccine (Day 28); 0.5 mL IM (Day 0); ≥4.0 Log10 PFU SC (Day 28); Other Names: ChimeriVax™-JE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Solicited Injection Site and Systemic Reactions After Injection With Either JE-CV or Hepatitis A Vaccine as First Injection	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.	Day 0 up to Day 14 post-vaccination
Number of Participants With Solicited Injection Site and Systemic Reactions After Injection With Either JE-CV or Hepatitis A Vaccine as Second Injection	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.	Day 0 up to Day 14 post-vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Seroconversion to JE-CV Vaccine Antigens Following Administration of JE-CV 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.	Day 0 (pre-vaccination) and Day 28 after final vaccination
Summary of Geometric Mean Titers Against JE Antibodies Before and After JE-CV Vaccination	JE virus neutralizing antibody measurement was assessed by the PRNT50 assay.	Day 0 (pre-vaccination) and Day 28 after final vaccination

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Summary of Persistence of Seroprotection to JE-CV Antigens Up To Five Years Following Vaccination	Japanese Encephalitis virus neutralizing antibody measurement was assessed by the PRNT50 assay.	Day 0 (pre-vaccination) up to 5 years after final vaccination
Summary of Geometric Mean Titer Against JE Antibodies Up To Five Years Following Vaccination With JE-CV Vaccine	Japanese Encephalitis virus neutralizing antibody measurement was assessed by the PRNT50 assay.	Day 0 (pre-vaccination) up to 5 years after final vaccination

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• Chokephaibulkit K, Sirivichayakul C, Thisyakorn U, Sabchareon A, Pancharoen C, Bouckenooghe A, Gailhardou S, Boaz M, Feroldi E. Safety and immunogenicity of a single administration of live-attenuated Japanese encephalitis vaccine in previously primed 2- to 5-year-olds and naive 12- to 24-month-olds: multicenter randomized controlled trial. Pediatr Infect Dis J. 2010 Dec;29(12):1111-7. doi: 10.1097/INF.0b013e3181f68e9c.
• Feroldi E, Boaz M, Yoksan S, Chokephaibulkit K, Thisyakorn U, Pancharoen C, Monfredo C, Bouckenooghe A. Persistence of Wild-Type Japanese Encephalitis Virus Strains Cross-Neutralization 5 Years After JE-CV Immunization. J Infect Dis. 2017 Jan 15;215(2):221-227. doi: 10.1093/infdis/jiw533.
• Chokephaibulkit K, Sirivichayakul C, Thisyakorn U, Pancharoen C, Boaz M, Bouckenooghe A, Feroldi E. Long-term follow-up of Japanese encephalitis chimeric virus vaccine: Immune responses in children. Vaccine. 2016 Nov 4;34(46):5664-5669. doi: 10.1016/j.vaccine.2016.09.018. Epub 2016 Sep 27.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: February 12, 2008
• First Submitted That Met QC Criteria: February 21, 2008
• First Posted (Estimate): February 22, 2008

Study Record Updates

• Last Update Posted (Estimate): October 2, 2014
• Last Update Submitted That Met QC Criteria: September 23, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Hepatitis A; Japanese encephalitis (JE); Inactivated Mouse-Brain
• Additional Relevant MeSH Terms: Digestive System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Liver Diseases; Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infectious Encephalitis; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Encephalitis, Japanese; Encephalitis; Hepatitis; Hepatitis A; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: JEC01