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

Dengue Fever Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02827162
• Other study ID #: CYD59
• Secondary ID: U1111-1127-7875
• Status: Completed
• Start date: March 29, 2016
• Est. completion date: April 27, 2016

Study information

• Verified date: April 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 334
• Est. completion date: April 27, 2016
• Est. primary completion date: April 27, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 7 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Dengue
• Dengue Fever
• Dengue Haemorrhagic Fever
• Fever
• Hyperthermia
• Severe Dengue

Locations

Country	Name	City	State
Thailand	Investigational Site	Ratchaburi

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company

Country where clinical trial is conducted

Thailand, 

References & Publications (1)

Geretz A, Ehrenberg PK, Bouckenooghe A, Fernández Viña 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: 10.1 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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	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	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 3 up to 4 years (end of the Active phase)
Secondary	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)