Safety and Efficacy Study of ChimeriVax™-JE and JE Inactivated Mouse Brain Vaccine in Children of Descending Age

Randomised, Double Blind, Controlled, Safety, Tolerability and Immunogenicity Phase II Trial of ChimeriVax™-JE and Japanese Encephalitis Inactivated Mouse Brain Vaccine in Children of Descending Age.

This randomised, double-blind study is to be conducted on 96 subjects at multiple sites in India. Subjects will be enrolled by age group and randomised to either ChimeriVax™-JE (JE-CV) or JE Mouse Brain Derived Vaccine (JE-MBDV). Study consists of a screening period, a treatment period and a 2 year follow-up period.

Primary safety endpoints will be the adverse event (AE) rates 28 days after completion of vaccination course. The primary efficacy endpoints will be the rate of seroconversion 28 days after completing vaccination.

Study Overview

• Status: Completed
• Conditions: Japanese Encephalitis
• Intervention / Treatment: Biological: ChimeriVax™-JE; Biological: Japanese Encephalitis Inactivated Mouse Brain Vaccine

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • Baroda, India, 390001
    • Government Medical College
  • New Delhi, India, 110002
    • Maulana Azad Medical College
  • Rajasthan
    • Jaipur, Rajasthan, India, 302016
      • Dr Atul's Child Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 8 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All aspects of the Protocol explained and written informed consent obtained from the subject's parent or guardian and assent from the child if ≥ 8 years of age.
• Aged ≥ 9 months to < 10 years
• In good general health, without significant medical history, physical examination findings, or clinically significant abnormal laboratory results
• Subject had to be available for the study duration for the study duration, including all planned follow-up visits.

Exclusion Criteria:

• A history of vaccination against, or infection with, JE or other flaviviruses (e.g. Kyanasur Forest Disease, West Nile virus, dengue fever). Previous JE vaccination was to be determined by history (interview of subject's parent or guardian) or by inspecting the child's official vaccination record.
• Demonstration of parasitemia on malaria blood smear at Screening.
• History of residence in or travel to a JE-endemic region of India or elsewhere in Asia (for periods of 4 weeks or more).
• hypersensitivity to thimerosal or gelatin
• Have received a transfusion of blood, blood products or serum globulin in the preceding 6 months,
• Have an immunodeficiency or neurological disorder, or take drugs that suppress the immune system,
• Have a history of severe reaction to other vaccines,
• Have a chronic condition requiring medication,
• Intend to travel out of the area during the study period,
• Have spent at least 4 weeks in a JE-endemic region,
• Plan to receive any other vaccination within the double-blind treatment period, or who have received a vaccination in the month preceding Screening,
• Exhibit signs of secondary or tertiary malnutrition,
• Are seropositive to human immunodeficiency virus (HIV), Hepatitis B or C,
• Have malaria infection, or who have a fever within 3 days before vaccination.
• Those with an acute fever, or with previously scheduled vaccinations, may be rescheduled.
• Consideration of the routine immunisation schedule should be made such that it is ensured that routine vaccinations due are either given before entry to the trial, or afterwards if delayed because of the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JE-CV Group; Participants will receive Japanese encephalitis chimeric virus vaccine (JE-CV)	Biological: ChimeriVax™-JE; One dose of 4.0 log10 PFU is given in a volume of 1 ml for children aged > 3 years and 0.5 ml to children and infants aged < 3 years administered subcutaneously
Active Comparator: MBDV Group; Participants will receive the mouse brain-derived vaccine (MBDV)	Biological: Japanese Encephalitis Inactivated Mouse Brain Vaccine; Two doses of 1 ml reconstituted JE-MBDV is given to subjects aged > 3 years and 0.5 ml is given to children and infants aged < 3 years administered subcutaneously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events Following Vaccination With Either ChimeriVax™ JE or JE Inactivated Mouse Brain Derived Vaccine		Day 14 up to Day 42 Post-vaccination
Number of Participants With Treatment-Related Adverse Events Following Vaccination With Either ChimeriVax™ JE or JE Inactivated Mouse Brain Derived Vaccine		Day 14 up to Day 42 Post-vaccination
Number of Participants With Seroconversion After Vaccination With Either ChimeriVax™ JE or JE Inactivated Mouse Brain Derived Vaccine	Antibodies to Japanese encephalitis (JE) virus were measured with 50% plaque reduction neutralization tests (PRNT50) using JE CV virus, JE virus Nakayama strain, and JE virus strain 826309 (Indian wild-type). Seroconversion was defined as a titer ≥10 1/dil for participants who were seronegative at baseline and ≥ 4 fold rise for participants who were seropositive at baseline (titer ≥ 10 1/dil).	Day 42 Post-vaccination
Geometric Mean Titers (GMTs) of Japanese Encephalitis Viruses After Vaccination With Either ChimeriVax™ JE or JE Inactivated Mouse Brain Derived Vaccine	Antibodies to Japanese encephalitis (JE) virus were measured with 50% plaque reduction neutralization tests (PRNT50) using JE CV virus, JE virus Nakayama strain, and JE virus strain 826309 (Indian wild-type).	Day 42 Post Dose 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Seroconversion After Vaccination With Either ChimeriVax™ JE or JE Inactivated Mouse Brain Derived Vaccine	Antibodies to Japanese encephalitis (JE) virus were measured with 50% plaque reduction neutralization tests (PRNT50) using JE CV virus, JE virus Nakayama strain, and JE virus strain 826309 (Indian wild-type). Seroconversion was defined as a titer ≥10 1/dil for participants who were seronegative at baseline and ≥ 4 fold rise for participants who were seropositive at baseline (titer ≥ 10 1/dil).	Day 42 Post Dose 1
Geometric Mean Titers (GMTs) Using Neutralizing Antibody to Japanese Encephalitis Viruses After Vaccination With Either ChimeriVax™ JE or JE Inactivated Mouse Brain Derived Vaccine	Antibodies to Japanese encephalitis (JE) virus were measured with 50% plaque reduction neutralization tests (PRNT50) using JE CV virus, JE virus Nakayama strain, and JE virus strain 826309 (Indian wild-type).	Day 42 Post-vaccination

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Principal Investigator: Anand Dubey, M.D, Maulana Azad Medical College, New Delhi, India; Principal Investigator: Bakul B. Javadekar, M.D., Government Medical College, Baroda, India; Principal Investigator: Atul Shanker, Dr., Dr Atul's Child Hospital, Jaipur, Rajasthan, India

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: February 27, 2007
• First Submitted That Met QC Criteria: February 27, 2007
• First Posted (Estimate): February 28, 2007

Study Record Updates

• Last Update Posted (Estimate): August 27, 2012
• Last Update Submitted That Met QC Criteria: July 24, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Japanese Encephalitis
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infectious Encephalitis; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Encephalitis, Japanese; Encephalitis
• Other Study ID Numbers: H-040-004