Clinical Trial: Study of a Novel Tetravalent Dengue Vaccine in Healthy Children Aged 2 to 14 Years in Asia

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Efficacy and Safety of a Novel Tetravalent Dengue Vaccine in Healthy Children Aged 2 to 14 Years in Asia

Brief Summary:

The aim of this trial is to assess the efficacy of the CYD dengue vaccine in preventing symptomatic, virologically-confirmed dengue cases.

Primary Objective:

To assess the efficacy of CYD dengue vaccine after 3 vaccinations at 0, 6, and 12 months in preventing symptomatic virologically-confirmed dengue cases, regardless of the severity, due to any of the four serotypes in children aged 2 to 14 years at the time of inclusion.

Secondary Objectives:

To describe the efficacy of CYD dengue vaccine after each dose in:

  • Preventing symptomatic virologically-confirmed dengue cases due to any of the four serotypes
  • Preventing symptomatic dengue cases, either virologically-confirmed or probable based on serological criteria, due to any of the four serotypes

To describe the occurrence of serious adverse events (SAEs), including serious adverse events of special interest in all subjects throughout the trial period.


Detailed Summary:

Participants will be randomized to either receive 3 injections of CYD dengue vaccine or a placebo at 0, 6, and 12 months.

A subset of participants from each country will also be evaluated for reactogenicity and immunogenicity to enable the generation of country-specific data on reactogenicity, immunogenicity, and baseline dengue and JE antibody levels.


Sponsor: Sanofi Pasteur, a Sanofi Company

Current Primary Outcome:

  • Number of Symptomatic Virologically Confirmed Dengue Cases (Vaccine Efficacy) Due to Any Serotype During the Active Phase Post-dose 3 Injection With CYD Dengue Vaccine [ Time Frame: 28 days and up to 13 months post-injection 3 ]

    Symptomatic virologically-confirmed dengue (VCD) cases were defined as acute febrile illness (temperature ≥38°C on at least 2 consecutive days) and confirmed by dengue reverse transcriptase polymerase chain reaction and/or dengue NS1 enzyme-linked immunosorbent assay. Cases defined as number of subjects with at least one symptomatic VCD episode from 28 days post-injection 3 to the end of Active Phase.

    The vaccine efficacy is considered as significant if the lower bound of its 95% CI (exact method by Breslow & Day) is greater than 25%.

  • The Person-years at Risk for Participants With Symptomatic Virologically Confirmed Dengue Cases (Vaccine Efficacy) Due to Any Serotype During the Active Phase Post-dose 3 Injection With CYD Dengue Vaccine [ Time Frame: 28 days and up to 14 months post-injection 3 ]
    The person-years at risk was the cumulative time (in years) until the participant was diagnosed with VCD or until the end of the active period, whichever came first. Data presented is the sum of individual units of time for which the participants contributed to the analyses. Incidence density was calculated as the number of VCD cases divided by the cumulative person-years at risk. The vaccine efficacy is considered as significant if the lower bound of its 95% CI (exact method by Breslow & Day) is greater than 25%.
  • Density Incidence of Symptomatic Virologica

    Original Primary Outcome: Information on the symptomatic virologically confirmed dengue cases occurring > 28 days after Dose 3 (during the active phase) in terms of (i) Acute febrile illness, and (ii) Virologically confirmed [ Time Frame: 28 Days post-vaccination 3 ]

    Current Secondary Outcome:

    • Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With CYD Dengue Tetravalent Vaccine [ Time Frame: Pre-vaccination 1 and Day 28 post each vaccination up to 25 months (visit 07) ]
      Geometric mean titers against each serotypes of the Dengue virus strains were assessed using the plaque reduction neutralization test (PRNT) in a pre-defined subset of 2,000 subjects from each country (1,333 in the CYD Dengue Vaccine Group and 667 in the Control Group).
    • Percentage of Flavi Virus-Immuned Participants at Baseline With Antibody Titers ≥10 1/Dil Against Each Parental Dengue Virus Serotype Strain Before and Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine [ Time Frame: Pre-vaccination 1 and Day 28 post each vaccination up to 25 months (visit 07) ]
      Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Flavi virus (FV) immune participants at baseline are defined as those participants with ≥ 10 1/dil for at least one serotype with the parental dengue virus strain or for Yellow Fever titer.
    • Percentage of Subjects With Solicited Injection-site and Systemic Reactions Following Any and Each Injection With CYD Dengue Tetravalent Vaccine [ Time Frame: Day 0 up to Day 14 post each vaccination ]
      Solicited injection-site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever (Temperature), Headache, Malaise, Myalgia, and Asthenia. Grade 3 Solicited injection site reactions (2-11 years): Pain, Incapacitating, unable to perform usual activities; Erythema and Swelling, ≥50 mm. Grade 3 Solicited injection site reactions (12-14 years): Pain, Significant, prevents daily activity; Erythema and Swelling, >100 mm. Grade 3 Solicited injection site reactions: Fever, ≥39°C; Headache, Malaise, Myalgia, and Asthenia, Significant, prevents daily activity.


    Original Secondary Outcome:

    • Information on the occurrence of serious adverse events (SAEs), including SAEs of special interest in all subjects throughout the trial period [ Time Frame: Day 0 up to 12 months post vaccination ]
    • Information on the efficacy of CYD dengue vaccine in preventing symptomatic dengue cases either virologically confirmed or probable based on serological criteria, due to any of the four serotypes after each dose. [ Time Frame: 28 Days after each vaccination ]


    Information By: Sanofi

    Dates:
    Date Received: June 8, 2011
    Date Started: June 2011
    Date Completion: November 2017
    Last Updated: March 24, 2016
    Last Verified: March 2016