Clinical Trial: Association of Host Genetics With Vaccine Efficacy and Study of Immune Correlates of Risk From a Tetravalent Dengue Vaccine

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

Official Title: Association of Host Genetics With Vaccine Efficacy, and Evaluation of Immune Correlates of Risk From the First Proof of Concept Efficacy Study With a Tetravalent Dengue Vaccine

Brief Summary:

Primary objectives:

  • To assess how dengue vaccine efficacy varies across participant subgroups regarding polymorphism in human leukocyte antigen (HLA) alleles of interest.
  • To assess the association between HLA alleles and, serotype-specific neutralization antibody titers and summary neutralization measure in the vaccine and placebo groups.
  • To assess the association between the polymorphism in HLA alleles of interest and susceptibility to Dengue fever and Dengue Haemorrhagic fever.

Secondary objectives:

  • To assess whether dengue serotype-specific neutralizing antibody titers and associated summary neutralization measure at 28 days post-dose 3 are related to the rate of occurrence of symptomatic Virologically-confirmed dengue infection after post-dose 3
  • To evaluate whether the dengue serotype-specific neutralizing antibody and associated summary neutralization measure at 28 days post-dose 3 are related to the level of vaccine efficacy against dengue viruses after post-dose 3.

Detailed Summary:

The enrolled population will include both, virologically-confirmed (VC) dengue cases and subjects not having experienced a VC dengue infection (control subjects) from the first Proof of Concept efficacy study conducted in Thailand Analyses for correlates will be performed on samples collected in the context of the first proof of concept efficacy study. Sequencing of dengue viruses will also be done on samples collected within the same context. Immunogenetic testing will be performed on saliva samples collected at the study enrollment visit.

No intervention or vaccine will be provided or administered as part of this study.


Sponsor: Sanofi Pasteur, a Sanofi Company

Current Primary Outcome:

  • Number of Symptomatic Virologically confirmed dengue cases having occurred during the Active Phase of the first proof of concept efficacy study after post dose 1 [ Time Frame: 28 days post-injection 1 up to 4 years (the end of the Active phase) ]
    A symptomatic Virologically confirmed (VC) dengue case is defined as (i) Acute febrile illness with fever lasting for at least 1 day (temperature ≥37.5°C measured at least twice with an interval of at least 4 hours), and (ii) VC by reverse transcriptase polymerase chain reaction (RT PCR) and / or dengue non structural protein 1 (NS1) enzyme linked immunosorbent assay (ELISA) Antigen test
  • Neutralizing Antibody level against each of the four parental dengue virus serotype strains of Sanofi Pasteur's dengue vaccine constructs measured at 28 days post dose 3 [ Time Frame: 28 days post-dose 3 (1 year post-dose 1) ]
  • Number of probable Dengue fever and Dengue Hemorrhagic Fever grade I, II, III, and IV occurring during the Active Phase of the first PoC efficacy study after post dose 1. [ Time Frame: Up to 6 months post-dose 1 ]
    Probable Dengue fever is an acute febrile illness with two or more of the following manifestations: Headache, Retro orbital pain, Myalgia, Arthralgia, Rash, Haemorrhagic manifestations, and Leukopaenia


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Number of Symptomatic Virologically confirmed dengue cases having occurred during the Active Phase of the first proof of concept efficacy study after post dose 3 [ Time Frame: 28 days post-injection 3 up to 4 years (end of the Active phase) ]
    A symptomatic Virologically confirmed (VC) dengue case is defined as (i) Acute febrile illness with fever lasting for at least 1 day (temperature ≥37.5°C measured at least twice with an interval of at least 4 hours), and (ii) VC by reverse transcriptase polymerase chain reaction (RT PCR) and / or dengue non structural protein 1 (NS1) enzyme linked immunosorbent assay (ELISA) Antigen test
  • Neutralizing Antibody level against each of the four parental dengue virus serotype strains of Sanofi Pasteur's dengue vaccine constructs measured at post dose 3 [ Time Frame: Post-dose 3 (1 year post-dose 1) ]


Original Secondary Outcome: Same as current

Information By: Sanofi

Dates:
Date Received: June 29, 2016
Date Started: March 2016
Date Completion: January 2018
Last Updated: April 25, 2017
Last Verified: April 2017