A Study of Japanese Encephalitis Chimeric Virus Vaccine Compared With SA14-14-2 Vaccine in Infants and Toddlers

• ClinicalTrials.gov Identifier: NCT01092507
• Recruitment Status: Completed
• First Posted: March 25, 2010
• Results First Posted: December 2, 2013
• Last Update Posted: December 25, 2013
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Tracking Information

• First Submitted Date: March 23, 2010
• First Posted Date: March 25, 2010
• Results First Submitted Date: September 30, 2013
• Results First Posted Date: December 2, 2013
• Last Update Posted Date: December 25, 2013
• Study Start Date: March 2010
• Actual Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 30, 2013)

Number of Participants With Japanese Encephalitis Seroconversion After Vaccination With One Dose of Either Japanese Encephalitis Chimeric Vaccine (JE-CV) or Japanese Encephalitis Live Vaccine (SA14-14-2) (CD.JEVAX®) [ Time Frame: Day 0 through Day 28 after vaccination ]

Immunogenicity was assessed by the JE-CV virus and the SA14-14-2 virus 50% plaque reduction neutralization test (PRNT50). Japanese Encephalitis seroconversion was defined as a pre-vaccination titer <10 1/dil and post-vaccination titer ≥ 10 1/dil; or a pre-vaccination titer ≥ 10 1/dil and a 4-fold increase from pre- to post-vaccination.

• Original Primary Outcome Measures (submitted: March 24, 2010): Immunogenicity in terms of seroconversion post-vaccination with Japanese encephalitis chimeric virus vaccine. [ Time Frame: 28 days post-vaccination ]

Current Secondary Outcome Measures (submitted: September 30, 2013)

• Number of Participants With Japanese Encephalitis Seroprotection 28 Days After Vaccination With One Dose of Either Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) or Japanese Encephalitis Live Vaccine (SA14-14-2, CD.JEVAX®) [ Time Frame: Day 28 post-vaccination ]
  Immunogenicity was assessed by JE-CV virus 50% plaque reduction neutralization test (PRNT50) or SA14-14-2 virus PRNT50. Japanese encephalitis seroprotection defined as participant with antibody titer ≥ 1:10 at baseline (D0) and on Day 28, Month 6, and Month 12.
• Number of Participants With Seroconversion After Vaccination With Either Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) or Japanese Encephalitis Live Vaccine (SA14-14-2) (CD.JEVAX®) [ Time Frame: Day 28 post-vaccination ]
  Immunogenicity was assessed by JE-CV virus 50% plaque reduction neutralization test (PRNT50) or SA14-14-2 virus PRNT50. Seroconversion was defined as a pre-vaccination titer < 10 1/dil and post vaccination titer ≥ 10 1/dil, or a pre-vaccination titer ≥ 10 and a 4-fold increase from pre- to post-vaccination.
• Summary of Geometric Mean Titers of Vaccine Antibodies Before and Following One Dose of Vaccination With Either Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) or Japanese Encephalitis Live Vaccine (SA14-14-2; CD.JEVAX®) [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ]
  Immunogenicity was assessed by JE-CV virus 50% plaque reduction neutralization test (PRNT50) or SA14-14-2 virus PRNT50.
• Summary of Participants With Japanese Encephalitis Seroprotection After Vaccination With One Dose of Either Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) or Japanese Encephalitis Live Vaccine (SA14-14-2, CD.JEVAX®) [ Time Frame: Day 28 up to 12 months post-vaccination ]
  Immunogenicity was assessed by JE-CV virus 50% plaque reduction neutralization test (PRNT50) or SA14-14-2 virus PRNT50. Japanese encephalitis seroprotection defined as participant with antibody titer ≥ 1:10 at baseline (D0) and on Day 28, Month 6, and Month 12.
• Summary of Geometric Mean Titers of Vaccine Antibodies Before and Following One Dose of Vaccination With Either Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) or Japanese Encephalitis Live Vaccine (SA14-14-2; CD.JEVAX®) [ Time Frame: Day 0 (pre-vaccination) and up to 12 months post-vaccination ]
  Immunogenicity was assessed by JE-CV virus 50% plaque reduction neutralization test (PRNT50) or SA14-14-2 virus PRNT50.
• Number of Participants Reporting a Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) or Japanese Encephalitis Live Vaccine (SA14-14-2 Vaccine) (CD.JEVAX®) [ Time Frame: Day 0 through Day 14 post-vaccination ]
  Solicited Injection Site Reactions: Tenderness, Erythema, Swelling. Solicited Systemic Reactions: Fever (Temperature), Vomiting, Crying Abnormal, Drowsiness, Appetite Loss, Irritability. Grade 3 Reactions defined as: Tenderness - crying when injected limb was moved, or movement of the injected limb was reduced; Erythema and Swelling - ≥ 5 cm; Fever - temperature > 39.5ºC; Vomiting - ≥ 6 episodes per 24 hours or requiring parenteral hydration; Crying Abnormal - > 3 hours; Drowsiness - Sleeping most of the time or difficult to wake up; Appetite loss - refused ≥ 3 feeds or refused most feeds; and Irritability - inconsolable.

• Original Secondary Outcome Measures (submitted: March 24, 2010): Safety in terms of solicited injection site and systemic events, and serious adverse events (SAEs) after primary administration of Japanese encephalitis chimeric virus vaccine. [ Time Frame: 0-14 days and up to 12 months post-vaccination ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Japanese Encephalitis Chimeric Virus Vaccine Compared With SA14-14-2 Vaccine in Infants and Toddlers
• Official Title: A Controlled Study of the Immunogenicity and Safety of Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) in Comparison With SA14-14-2 Vaccine in Infants and Toddlers in Thailand

Brief Summary

The purpose of this study is to compare a single dose of Japanese encephalitis (JE) chimeric virus vaccine (JE-CV) with a single dose of SA14-14-2 live vaccine as primary vaccination in infants and toddlers.

Primary Objective:

• To demonstrate the non-inferiority of the antibody response 28 days after vaccine administration of one dose of JE CV (administered on Day 0) compared to the antibody response after one dose of the SA14-14-2 control vaccine (administered on Day 0).

Secondary Objectives:

• To describe the immune response to JE in both vaccine groups in JE-CV virus and SA14-14-2 virus before and after a single dose of JE CV or a single dose of SA14-14-2 vaccine
• To describe the safety profile in all vaccinated subjects up to 28 days and all serious adverse events (SAEs) up to 6 months after vaccination.
• To describe only related SAEs and all death from 6 month to 12-month follow-up.

• Detailed Description: All participants will receive one injection of their randomized vaccine on Day 0. Follow-up will continue for 12 months after vaccination.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention

Condition

• Encephalitis
• Japanese Encephalitis

Intervention

• Biological: Japanese encephalitis chimeric virus vaccine (JE-CV)
  0.5 mL, Subcutaneous
• Biological: Japanese encephalitis live vaccine (SA14-14-2 vaccine) (CD.JEVAX®)
  0.5 mL, Subcutaneous

Study Arms

• Experimental: JE-CV Group
  Participants will receive one dose of Japanese encephalitis chimeric virus vaccine (JE-CV)
  Intervention: Biological: Japanese encephalitis chimeric virus vaccine (JE-CV)
• Active Comparator: SA14-14-2 vaccine Group
  Participants will receive one dose of Japanese encephalitis live vaccine, SA14-14-2 vaccine. (CD.JEVAX®)
  Intervention: Biological: Japanese encephalitis live vaccine (SA14-14-2 vaccine) (CD.JEVAX®)

• Publications *: Feroldi E, Pancharoen C, Kosalaraksa P, Chokephaibulkit K, Boaz M, Meric C, Hutagalung Y, Bouckenooghe A. Primary immunization of infants and toddlers in Thailand with Japanese encephalitis chimeric virus vaccine in comparison with SA14-14-2: a randomized study of immunogenicity and safety. Pediatr Infect Dis J. 2014 Jun;33(6):643-9. doi: 10.1097/INF.0000000000000276.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 24, 2010): 300
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: October 2011
• Actual Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria :

• Aged 9 to 18 months on the day of inclusion
• In good general health, without significant medical history
• Provision of informed consent form signed by at least one parent or other legally acceptable representative, and by at least one independent witness if required by local regulations
• Subject and parent/legally acceptable representatives able to attend all scheduled visits and comply with all trial procedures
• Completion of vaccinations according to the national immunization schedule.

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
• 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 corticosteroid therapy
• 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
• 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
• Previous vaccination against flavivirus disease, including Japanese encephalitis (JE)
• Administration of any anti-viral within 2 months preceding first vaccination and up to the 4 weeks following the last trial vaccination at Month 3
• Receipt of any vaccine in the 4 weeks preceding the first trial vaccination
• Planned receipt of any vaccine from the inclusion up to the 4 weeks following the last trial vaccination
• Planned receipt of any Japanese encephalitis vaccine during the course of the study
• History of central nervous system disorder or disease, including seizures
• History of flavivirus infection (confirmed either clinically, serologically or microbiologically)
• Febrile illness (temperature ≥ 38°C) or moderate or severe acute illness/infection on the day of vaccination, according to Investigator judgment.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 9 Months to 18 Months (Child)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Thailand

Administrative Information

• NCT Number: NCT01092507
• Other Study ID Numbers: JEC07; UTN: U1111-1112-2269 ( Other Identifier: WHO )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
• Original Responsible Party: Medical Director, Sanofi Pasteur Inc.
• Current Study Sponsor: Sanofi Pasteur, a Sanofi Company
• Original Study Sponsor: Sanofi
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Sanofi Pasteur Inc.

• PRS Account: Sanofi
• Verification Date: November 2013