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

NCT06805487 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CIR 369
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Zika Virus

Outcome Measures

Primary Outcomes (6)

• Incidence, magnitude, and duration of infectious ZIKV-SJRP/2016-184 recovered from serum following administration of ZIKV-SJRP/2016-184 in subjects who received TV003

  Compared to historical controls

  Through 180 days post challenge

• Incidence, magnitude, and duration of infectious ZIKV-SJRP/2016-184 recovered from serum following administration of ZIKV-SJRP/2016-184 in ZIKV-exposed subjects

  Compared to historical controls

  Through 180 days post challenge

• Proportion of subjects who received TV003 who develop clinical signs/symptoms of Zika infection

  Compared to historical controls

  Through 180 days post challenge

• Proportion of subjects who were previously infected with ZIKV who develop clinical signs/symptoms of Zika infection

  Compared to historical controls

  Through 180 days post challenge

• Frequency of immediate, systemic, and local adverse events (AEs) following vaccination with TV003

  Through 28 days post vaccination

• Frequency of immediate, systemic, and local AEs following inoculation with ZIKV-SJRP/2016-184

  Through 28 days post challenge

Secondary Outcomes (10)

• Incidence, magnitude, and duration of ZIKV viremia induced by administering 10^2 PFU of ZIKV-SJRP/2016-184 in subjects who received TV003

  Through 6 months post challenge

• Incidence, magnitude, and duration of ZIKV viremia induced by administering 10^2 PFU of ZIKV-SJRP/2016-184 in previously ZIKV-exposed subjects

  Through 6 months post challenge

• Number of TV003 vaccinees infected with DENV-1, DENV-2, DENV-3, and DENV-4 following administration of TV003

  Through 270 days post vaccination

• Peak neutralizing antibody titer (NT) to DENV-1, DENV-2, DENV-3, and DENV-4

  Through 90 days post vaccination

• Peak NT to ZIKV-SJRP/2016-184

  Through 90 days post challenge

Study Arms (3)

Arm 1: DENV/ZIKV naive subjects receiving TV003

EXPERIMENTAL

Twelve volunteers will receive TV003 followed by challenge with ZIKV on Day 180 (6 months post-vaccination).

Biological: TetraVax-DV-TV003 (TV003); Biological: Challenge virus ZIKV-SJRP/2016-184

Infectivity Controls: DENV/ZIKV naive subjects receiving PlasmaLyte

PLACEBO COMPARATOR

Four volunteers will receive PlasmaLyte as control followed by challenge with ZIKV at least 28 days after vaccination.

Biological: Plasmalyte; Biological: Challenge virus ZIKV-SJRP/2016-184

Arm 2: Subjects with previous ZIKV infection

EXPERIMENTAL

Previous ZIKV-infected volunteers will be challenged with ZIKV on Arm 2 Day 0.

Biological: Challenge virus ZIKV-SJRP/2016-184

Interventions

TetraVax-DV-TV003 (TV003) BIOLOGICAL

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

Arm 1: DENV/ZIKV naive subjects receiving TV003

Plasmalyte BIOLOGICAL

0.5 mL of PlasmaLyte delivered via subcutaneous injection

Infectivity Controls: DENV/ZIKV naive subjects receiving PlasmaLyte

Challenge virus ZIKV-SJRP/2016-184 BIOLOGICAL

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).

Arm 1: DENV/ZIKV naive subjects receiving TV003; Arm 2: Subjects with previous ZIKV infection; Infectivity Controls: DENV/ZIKV naive subjects receiving PlasmaLyte

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adults between 18 and 40 years of age, inclusive.
• Good general health as determined by physical examination, laboratory screening, and review of medical history.
• Available for the duration of the study, approximately 52 weeks.
• Willingness to participate in the study as evidenced by signing the informed consent document.
• Must be able to complete the informed consent process and comprehension assessment independently and without assistance.
• Subjects assigned male at birth: Willingness to use barrier contraception during cervico-vaginal, anal, and oral intercourse from Study Day 0 through 90 days post ZIKV challenge (in accordance with CDC guidance).
• Subjects assigned female at birth: Willingness to use barrier contraception during cervico-vaginal, anal, and oral intercourse from Study Day 0 through 56 days post ZIKV challenge (in accordance with CDC guidance).
• Subjects of childbearing potential must be willing to use effective contraception through 56 days post-ZIKV challenge, in accordance with CDC guidance. Reliable methods of contraception include hormonal birth control\* (implantable, hormonal patch, hormonal vaginal ring, oral contraception, Depo-Provera injection, etc.), surgical sterilization (hysterectomy, tubal ligation, or tubal coil at least 3 months prior to inoculation with TV003/PlasmaLyte and/or ZIKV challenge), and intrauterine device. All subjects assigned female at birth will be considered having child-bearing potential except for those with post-menopausal status documented as at least 1 year since last menstrual period, those assigned female at birth who have sex with partners assigned female at birth (exclusively) and have no intention of conceiving a child during the study, and for the vaccination phase of the study only, participants who practice abstinence (≥ 6 months with no sexual contact). Subjects who are not considered to be of childbearing potential will not be required to use contraception other than barrier contraception for the purpose of reducing potential transmission.
• Volunteers on hormonal birth control must not be on medications or other agents that decrease the effectiveness of hormonal birth control.
• Currently enrolled in the study.
• Good general health as determined by physical examination and review of medical history.
• Available for the duration of the study, which is approximately 26 weeks after challenge.
• If the challenge portion of the study is expected to begin from March 16-October 30, subject is willing to reside in the inpatient unit for 6 days (or longer for safety if necessary) following receipt of ZIKV.
• Willingness to participate in the study as evidenced by signing the informed consent document.
• Female assigned at birth only: Female assigned at birth subjects of childbearing potential should be willing to use highly effective contraception for the duration of the trial. Reliable methods of contraception include hormonal birth control, surgical sterilization, and intrauterine device. All female assigned at birth subjects will be considered as having childbearing potential in this phase of the study, except for those who have had a hysterectomy, tubal ligation, or tubal coil (at least 3 months prior to vaccination), or who are considered to be post-menopausal, as documented by at least 1 year since last menstrual period.

You may not qualify if:

• Currently pregnant, as determined by positive beta-human choriogonadotropin (b-hCG) test, breast-feeding, planning to become pregnant during the 12-month duration of the study or planning to donate eggs through 56 days post ZIKV challenge. A careful detailed reproductive and contraception use history will be obtained and the subject will be excluded if the history or clinical record raises concerns related to pregnancy prevention.
• Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies.
• Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and cooperate with the requirements of the study protocol.
• Evidence of recent opiate use based on urine toxicology screen.
• Screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC), ALT, and serum creatinine, as defined in this protocol.
• Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a subject participating in the trial or would render the subject unable to comply with the protocol.
• Any significant alcohol or drug abuse in the past 12 months which has caused medical, occupational, or family problems, as indicated by subject history.
• History of a severe allergic reaction or anaphylaxis.
• Severe asthma (emergency room visit or hospitalization within the last 6 months).
• HIV infection, by screening and confirmatory assays.
• Hepatitis C virus (HCV) infection, by screening and confirmatory assays.
• Hepatitis B virus (HBV) infection, by Hepatitis B surface antigen (HBsAg) screening.
• History of Guillain-Barré syndrome (GBS).
• History of seizure disease or peripheral neuropathy.
• History of any neuroinflammatory disorder, i.e., Bell's Palsy, transverse myelitis.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Johns Hopkins Bloomberg School of Public Health: collaborator

Study Sites (2)

Center for Immunization Research, Johns Hopkins School of Public Health

Baltimore, Maryland, 21205, United States

Location

Center for Immunization Research

Baltimore, Maryland, 21224, United States

Location

Related Publications (3)

• Pierce KK, Durbin AP, Walsh MR, Carmolli M, Sabundayo BP, Dickson DM, Diehl SA, Whitehead SS, Kirkpatrick BD. TV005 dengue vaccine protects against dengue serotypes 2 and 3 in two controlled human infection studies. J Clin Invest. 2024 Feb 1;134(3):e173328. doi: 10.1172/JCI173328.

  PMID: 37971871 BACKGROUND

• Durbin AP, Kirkpatrick BD, Pierce KK, Schmidt AC, Whitehead SS. Development and clinical evaluation of multiple investigational monovalent DENV vaccines to identify components for inclusion in a live attenuated tetravalent DENV vaccine. Vaccine. 2011 Sep 23;29(42):7242-50. doi: 10.1016/j.vaccine.2011.07.023. Epub 2011 Jul 21.

  PMID: 21781997 BACKGROUND

• Kallas EG, Cintra MAT, Moreira JA, Patino EG, Braga PE, Tenorio JCV, Infante V, Palacios R, de Lacerda MVG, Batista Pereira D, da Fonseca AJ, Gurgel RQ, Coelho IC, Fontes CJF, Marques ETA, Romero GAS, Teixeira MM, Siqueira AM, Barral AMP, Boaventura VS, Ramos F, Elias Junior E, Cassio de Moraes J, Covas DT, Kalil J, Precioso AR, Whitehead SS, Esteves-Jaramillo A, Shekar T, Lee JJ, Macey J, Kelner SG, Coller BG, Boulos FC, Nogueira ML. Live, Attenuated, Tetravalent Butantan-Dengue Vaccine in Children and Adults. N Engl J Med. 2024 Feb 1;390(5):397-408. doi: 10.1056/NEJMoa2301790.

  PMID: 38294972 BACKGROUND

MeSH Terms

Conditions

Zika Virus Infection

Interventions

Plasmalyte A

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections

Study Officials

• Anna Durbin, M.D.

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2025
• First Posted: February 3, 2025
• Study Start: September 24, 2024
• Primary Completion: September 15, 2025
• Study Completion: September 15, 2025
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)