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

NCT02827162 | Completed

• 2 other identifiers: CYD59U1111-1127-7875
• Study Type: observational
• Target: 334
• Locations: 1 country
• Sites: 1

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.

Conditions

Dengue Fever; Dengue Haemorrhagic Fever

Keywords

Dengue Fever; Dengue Haemorrhagic Fever; Tetravalent Dengue Vaccine

Outcome Measures

Primary Outcomes (3)

• 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

  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

  28 days post-injection 1 up to 4 years (the end of the Active phase)

• 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

  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.

  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

  Up to 6 months post-dose 1

Secondary Outcomes (2)

• 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

  28 days post-injection 3 up to 4 years (end of the Active phase)

• 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

  Post-dose 3 (1 year post-dose 1)

Study Arms (4)

Case D1

Subject having experienced a Virologically confirmed dengue infection, from the first injection until the end of the active phase, excluding Case D3 subjects

Case D3

Subject having experienced a Virologically confirmed dengue infection, from 28 days after the third injection until the end of the Active Phase of the proof of concept (PoC) efficacy study

Control I

Subject having not experienced a Virologically confirmed dengue infection in the Active Phase of the PoC efficacy study, and belonging to the PoC efficacy study immunogenicity subset

Control E

Subject having not experienced a Virologically confirmed dengue infection in the Active Phase of the PoC efficacy study, and not belonging to the PoC efficacy study immunogenicity subset

Eligibility Criteria

• Age: 7 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• 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

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (1)

Investigational Site

Ratchaburi, 70000, Thailand

Location

Related Publications (2)

• 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.

  PMID: 30243890 RESULT

• 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.

  PMID: 34635391 DERIVED

MeSH Terms

Conditions

Dengue

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Study Officials

• Medical Director

  Sanofi Pasteur SA

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2016
• First Posted: July 11, 2016
• Study Start: March 29, 2016
• Primary Completion: April 27, 2016
• Study Completion: April 27, 2016
• Last Updated: April 25, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share

Locations

TH (1)