Dengue Controlled Human Infection Model in Dhaka, Bangladesh

Dengue Clinical Trial

Official title: Phase II Evaluation of the Safety and Protective Efficacy of a Single Dose of the Live Attenuated Tetravalent Dengue Vaccine TetraVax-DV TV005 to Protect Against Infection With Live, Recombinant DENV-2 (rDEN2∆30-7169) Attenuated Strain in a Dengue Endemic Population in South Asia

Status Active, not recruiting

Clinical Trial Summary

The primary objective is to determine, among dengue-naïve adults in an endemic population, the protective efficacy of TetraVax-DV TV005 vaccine against dengue infection induced by a live recombinant attenuated rDEN2∆30-7169 attenuated virus strain administered 6, 12, or 24 months after vaccination.

Secondary objectives are:

1. Determine the durability of protection of TetraVax-DV TV005.

2. Evaluate the safety of TetraVax-DV TV005 in dengue-naïve volunteers in a dengue endemic population.

3. Evaluate the safety of the rDEN2∆30-7169 attenuated virus strain in a dengue endemic population.

Clinical Trial Description

This is a single center, Phase II, placebo-controlled, double-blind study to evaluate the ability of a single dose of TetraVax-DV TV005 vaccine to protect against infection induced by a live recombinant attenuated rDEN2∆30-7169 attenuated virus strain administered 6, 12, and 24 months after vaccination. TetraVax-DV TV005 will contain 103 PFU of rDEN1∆30, 104 PFU of rDEN2/4∆30(ME), 103 PFU of rDEN3∆30/31-7164 and 103 of rDEN4∆30. The dose of rDEN2∆30-7169 attenuated virus strain (DENV-2) will be 103 PFU. The placebo group will receive Plasma-Lyte A Injection pH 7.4.

The study population will be comprised of 192 healthy male and healthy non-pregnant, non-lactating female dengue-naïve adult volunteers aged 18-45 years, inclusive, from dengue-endemic Dhaka, Bangladesh. After providing written informed consent, volunteers will undergo eligibility screening, including medical history, physical examination, hematology testing, liver function testing, hepatitis B and C screening, and serology screening for previous dengue infection. Pregnancy testing will be performed on females with childbearing potential. All screening tests must be performed within 60 days prior to vaccination.

Eligible volunteers will be enrolled to receive TetraVax-DV TV005 or placebo (2:1) on an outpatient basis in one of three cohorts based on intended treatment with the attenuated virus strain timepoint (6, 12 or 24 months). The sequence of treatment assignments to either TV005 or placebo will be generated using block randomization. Randomization will occur sequentially at the time of study enrollment (vaccination) using a pre-generated list. All enrolled volunteers will be followed for 3 years post-vaccination for safety.

At 6, 12, and 24 months post-vaccination, volunteers will be re-screened for treatment with the attenuated virus strain with a live recombinant attenuated DENV-2 virus strain (rDEN2Δ30-7169). Volunteers will receive treatment with the attenuated virus strain in three separate treatment groups each consisting of 33 randomly-selected, eligible vaccine and placebo recipients (2:1) from the three independently vaccinated cohorts. Following treatment with the attenuated virus strain, designated study staff will make home visits to study participants to collect fever and AE information once per day up to day 16. A total of 66 vaccine and 33 placebo recipients (52% of enrolled population) will receive the attenuated virus strain.

Administration of the attenuated virus strain to volunteers at 12 and 24 months is contingent upon DSMB approval following review of all cumulative safety data from those volunteers treated with the attenuated virus strain at 6 months. Volunteers who receive placebo and are subsequently treated with the attenuated virus strain will be offered the TetraVax-DV TV005 vaccination 2 months after their attenuated virus strain dose. All volunteers who receive treatment with the attenuated virus strain will be followed for a minimum of one year post-treatment with the attenuated virus strain for safety (included in the overall 3 years of safety follow up).

Volunteers receiving treatment with the attenuated virus strain will be closely monitored following treatment with the attenuated virus strain and will be admitted to a local hospital for closer observation should they meet admission criteria. Administration of the attenuated virus strain to volunteers at 12 and 24 months is contingent upon DSMB approval following review of all cumulative safety data from those volunteers treated with the attenuated virus strain at 6 months. Volunteers who receive placebo and are subsequently treated with the attenuated virus strain will be offered the TetraVax-DV TV005 vaccination 2 months after their attenuated virus strain dose. All volunteers who receive treatment with the attenuated virus strain will be followed for a minimum of one year post-treatment with the attenuated virus strain for safety (included in the overall 3 years of safety follow up). ;

Related Conditions & MeSH terms

• Dengue

• NCT number: NCT05229354
• Study type: Interventional
• Source: University of Vermont
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 11, 2021
• Completion date: July 2025