Clinical trial NCT02827162: Association of Host Genetics With Vaccine Efficacy and Study of Immune Correlates of Risk From a Tetravalent Dengue Vaccine
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Dengue Fever
Dengue Haemorrhagic Fever
Keywords: Dengue Fever
Dengue Haemorrhagic Fever
Tetravalent Dengue Vaccine
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2016-07-11
Enrollment: 334
Sex: ALL
Minimum age (years): 7
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants 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 CYD57 (NCT01983553) conducted in Thailand

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 description: 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.

Eligibility criteria: Inclusion Criteria:

* Subject currently enrolled in, or having recently finished, CYD57 (NCT01983553; long-term safety follow-up study of the first PoC efficacy study), included in the subjects list provided by the Sponsor, with or without past experience of virologically confirmed dengue.
* For children 7 to \< 18 years. Assent form (AF) has been signed and dated by the subject, and informed consent form (ICF) has been signed and dated by the parents or another legally acceptable representative and by independent witness, as per local Ethics Committee (EC) requirement. For subjects ≥ 18 years. ICF has been signed and dated by the subject and by independent witness, as per local EC requirement.
* Subject (and parent(s) / legally acceptable representative for subject \< 18 years) are able to attend the scheduled visit and can comply with all study procedures.

Exclusion Criteria:

* Any illness that, in the opinion of the Investigator, might interfere with study procedures.

Primary outcomes:
measure: 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
timeFrame: 28 days post-injection 1 up to 4 years (the end of the Active phase)
measure: 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
timeFrame: 28 days post-dose 3 (1 year post-dose 1)
measure: 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.
timeFrame: Up to 6 months post-dose 1
Secondary outcomes:
measure: 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
timeFrame: 28 days post-injection 3 up to 4 years (end of the Active phase)
measure: 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
timeFrame: Post-dose 3 (1 year post-dose 1)
Other outcomes:
Locations:
city: Ratchaburi
country: Thailand
facility: Investigational Site
Study officials:
affiliation: Sanofi Pasteur SA
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Geretz A, Ehrenberg PK, Bouckenooghe A, Fernandez Vina MA, Michael NL, Chansinghakule D, Limkittikul K, Thomas R. Full-length next-generation sequencing of HLA class I and II genes in a cohort from Thailand. Hum Immunol. 2018 Nov;79(11):773-780. doi: 10.1016/j.humimm.2018.09.005. Epub 2018 Sep 19.
citation: Thomas R, Chansinghakul D, Limkittikul K, Gilbert PB, Hattasingh W, Moodie Z, Shangguan S, Frago C, Dulyachai W, Li SS, Jarman RG, Geretz A, Bouckenooghe A, Sabchareon A, Juraska M, Ehrenberg P, Michael NL, Bailleux F, Bryant C, Gurunathan S. Associations of human leukocyte antigen with neutralizing antibody titers in a tetravalent dengue vaccine phase 2 efficacy trial in Thailand. Hum Immunol. 2022 Jan;83(1):53-60. doi: 10.1016/j.humimm.2021.09.006. Epub 2021 Oct 8.