NCT06805487

Evaluation of the Protective Efficacy of TV003 or Previous Zika Infection Against Infection With ZIKV-SJRP Challenge Compared to DENV and ZIKV-naïve Controls Against Infection With ZIKV-SJRP Challenge

A Phase 1 Evaluation of the Protective Efficacy of a Single Dose of the Live Attenuated Tetravalent Dengue Vaccine TV003 or Previous Zika Infection Against Infection With ZIKV-SJRP Challenge Compared to DENV and ZIKV-naïve Historical Controls Against Infection With ZIKV-SJRP Challenge

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 40 Years
• Healthy volunteers: Accepted

Summary

Zika virus (ZIKV) is an illness people can get from mosquitoes. The infection is generally mild with symptoms that include a fever, rash, red eyes, and joint pain, though most of those infected have no symptoms. Preventing ZIKV is important because if a pregnant person is infected with ZIKV, it can cause birth defects in their unborn child. The goals of this study are to find out if people who have already been infected with one type of ZIKV can get infected with ZIKV a second time, and to test the ability of the TV003 dengue vaccine to prevent people from getting infected with the ZIKV-SJRP challenge virus.

Detailed description

This study is an open label with 2 study arms. Arm 1 will evaluate the protective efficacy of TV003 against ZIKV challenge. Arm 1 will include infectivity controls who will receive PlasmaLyte (the TV003 diluent) and the treatment assignment will be blinded to reduce bias in the assessment of adverse events. The PlasmaLyte recipients will serve as infectivity controls to ensure the potency of the ZIKV challenge. The treatment assignment of the infectivity controls may be unblinded as early as 28 days after receipt of TV003/PlasmaLyte if they are needed for ZIKV-challenge of volunteers in Arm 2 and may be challenged earlier than the TV003 cohort. Arm 2 will evaluate the protective efficacy of previous ZIKV infection against subsequent ZIKV challenge. Both arms will be compared to historical controls who previously received ZIKV infection. Infectivity controls will not be included in the efficacy analysis. This study will include 16 flavivirus-naïve subjects for Arm 1. Twelve subjects will receive the live attenuated dengue vaccine candidate TV003 at Study Day 0 and 4 subjects will receive PlasmaLyte at Study Day 0. These subjects will be randomized in blocks of 4 (3 TV003:1 PlasmaLyte). At Study Day 180, Arm 1 subjects will receive the controlled human infection strain of ZIKV SJRP/2016-184 as a challenge virus. These subjects will include those volunteers who received TV003 and at least 1 of the infectivity controls who received PlasmaLyte. Subjects in Arm 1 will be followed for approximately 52 weeks (approximately 360 days) from the time of vaccination. Ten subjects who had a ZIKV infection, either from a previous ZIKV controlled human infection study where they had received either ZIKV SJRP/2016-184 or ZIKV Nicaragua/2016 or were excluded during screening for previous studies as having ZIKV infection, will be enrolled as a group in Arm 2. Subjects enrolled in Arm 2 will be challenged with the ZIKV SJRP/2016-184 challenge virus separately from TV003 recipients. At least 1 of the PlasmaLyte recipients enrolled in Arm 1 on Day 0 will be included in this group to receive ZIKV SJRP/2016-184 as an infectivity control. Arm 2 subjects will be followed after ZIKV challenge for approximately 26 weeks (approximately 180 days). Subjects will be screened for eligibility up to 60 days prior to vaccination on Study Day 0.

Conditions

• Zika Virus

Interventions

Type	Name	Description
BIOLOGICAL	TetraVax-DV-TV003 (TV003)	0.5 ml of TV003 delivered via subcutaneous injection. TV003 contains 10\^3.3 plaque forming units (PFU)/mL of rDEN1Δ30, 10\^3.3 PFU/mL of rDEN2/4Δ30(ME), 10\^3.3 PFU/mL of rDEN3Δ30/31- 7164 and 10\^3.3 PFU/mL of rDEN4Δ30
BIOLOGICAL	Plasmalyte	0.5 mL of PlasmaLyte delivered via subcutaneous injection
BIOLOGICAL	Challenge virus ZIKV-SJRP/2016-184	0.5 ml of ZIKV-SJRP/2016-184 delivered via subcutaneous injection. ZIKV-SJRP/2016-184 contains a dose of 10\^2 plaque-forming units (PFU).

Timeline

• Start date: 2024-09-24
• Primary completion: 2025-09-15
• Completion: 2025-09-15
• First posted: 2025-02-03
• Last updated: 2026-03-09

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study