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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT00621764
First received: February 12, 2008
Last updated: September 23, 2014
Last verified: September 2014
  Purpose

Safety:

To describe the safety profiles following vaccination.

Immunogenicity:

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


Condition Intervention Phase
Japanese Encephalitis
Hepatitis A
Biological: Japanese encephalitis vaccine (Day 0) Hepatitis A vaccine (Day 28)
Biological: Hepatitis A vaccine (Day 0) Japanese encephalitis vaccine (Day 28)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Controlled Study of the Safety and Immunogenicity of ChimeriVax™ Japanese Encephalitis Vaccine in Thai Toddlers and Children

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Number of Participants With Solicited Injection Site and Systemic Reactions After Injection With Either JE-CV or Hepatitis A Vaccine as First Injection [ Time Frame: Day 0 up to Day 14 post-vaccination ] [ Designated as safety issue: No ]

    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 [ Time Frame: Day 0 up to Day 14 post-vaccination ] [ Designated as safety issue: No ]

    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:
  • Percentage of Participants With Seroconversion to JE-CV Vaccine Antigens Following Administration of JE-CV Vaccination [ Time Frame: Day 0 (pre-vaccination) and Day 28 after final vaccination ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 0 (pre-vaccination) and Day 28 after final vaccination ] [ Designated as safety issue: No ]
    JE virus neutralizing antibody measurement was assessed by the PRNT50 assay.


Other Outcome Measures:
  • Summary of Persistence of Seroprotection to JE-CV Antigens Up To Five Years Following Vaccination [ Time Frame: Day 0 (pre-vaccination) up to 5 years after final vaccination ] [ Designated as safety issue: No ]
    Japanese Encephalitis virus neutralizing antibody measurement was assessed by the PRNT50 assay.

  • Summary of Geometric Mean Titer Against JE Antibodies Up To Five Years Following Vaccination With JE-CV Vaccine [ Time Frame: Day 0 (pre-vaccination) up to 5 years after final vaccination ] [ Designated as safety issue: No ]
    Japanese Encephalitis virus neutralizing antibody measurement was assessed by the PRNT50 assay.


Enrollment: 300
Study Start Date: March 2008
Study Completion Date: May 2013
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 PFU SC (Day 0); 0.5 mL IM (Day 28)
Other Name: 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 Name: ChimeriVax™-JE

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.

  Eligibility

Ages Eligible for Study:   12 Months to 5 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00621764

Locations
Thailand
Bangkok, Thailand, 10700
Bangkok, Thailand, 10400
Bangkok, Thailand, 10330
Sponsors and Collaborators
Sanofi Pasteur, a Sanofi Company
Investigators
Study Director: Medical Director Sanofi Pasteur SA
  More Information

Publications:
Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00621764     History of Changes
Other Study ID Numbers: JEC01
Study First Received: February 12, 2008
Results First Received: September 9, 2014
Last Updated: September 23, 2014
Health Authority: Thailand: Food and Drug Administration

Keywords provided by Sanofi:
Japanese encephalitis (JE)
Hepatitis A
Inactivated Mouse-Brain

Additional relevant MeSH terms:
Encephalitis
Encephalitis, Japanese
Encephalitis, Arbovirus
Encephalitis, Viral
Hepatitis
Hepatitis A
Liver Diseases
Digestive System Diseases
Central Nervous System Viral Diseases
Virus Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Central Nervous System Infections
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Arbovirus Infections
Flavivirus Infections
Flaviviridae Infections

ClinicalTrials.gov processed this record on October 19, 2014