TetraVax-DV-TV003 for Zika Virus

Recruiting at 1 trial location

Overseen By Aislinn Woody, B.S.N., R.N.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Anticoagulants, Corticosteroids, Immunosuppressives, others

Disqualifiers: Pregnancy, HIV, Hepatitis B/C, others

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

26 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether individuals can contract the Zika virus (a mosquito-borne illness) more than once and if a dengue vaccine can help prevent it. Researchers will examine how the TetraVax-DV-TV003 vaccine works against the Zika virus. The study includes different groups: individuals who have never had Zika or dengue will receive either the vaccine or a placebo, while those who have had Zika before will be exposed to the virus again. Suitable participants may include those who have had Zika before or have never had Zika or dengue, are generally healthy, and are willing to participate for about a year. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new vaccine.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot use certain medications like corticosteroids or immunosuppressive drugs within 28 days before or after vaccination. If you are on anticoagulant medications, you may not be eligible to participate.

Is there any evidence suggesting that TetraVax-DV-TV003 is likely to be safe for humans?

Research has shown that the TetraVax-DV-TV003 vaccine is generally safe for people. Most study participants experienced only mild side effects, such as a rash or headache. Importantly, these studies reported no serious health problems. This suggests that the vaccine is safe for humans based on current data. This information may reassure those considering joining a clinical trial with this vaccine. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard of care for Zika virus, which often focuses on managing symptoms, TetraVax-DV-TV003 is a vaccine aimed at preventing the disease altogether. This investigational vaccine is unique because it is designed to elicit immunity against the Zika virus by using a live attenuated virus, which is a weakened form of the virus that can still provoke an immune response without causing the disease. Researchers are excited about TetraVax-DV-TV003 because it has the potential to provide long-lasting protection and reduce the risk of infection, which is particularly important in areas where Zika is prevalent. Additionally, the study includes a novel approach by testing the vaccine's effectiveness in individuals who have never been exposed to the virus as well as those who have previously had a Zika infection, offering insights into its broad applicability.

What evidence suggests that the TetraVax-DV-TV003 vaccine might be an effective treatment for Zika virus?

Research has shown that the TetraVax-DV-TV003 vaccine, initially developed for dengue, might also help prevent Zika virus infection. In studies, this vaccine triggered strong immune reactions, with all participants developing antibodies against the four types of dengue virus. This broad immune response suggests potential effectiveness against similar viruses, such as Zika. The vaccine demonstrated varying levels of protection against different dengue strains, with effectiveness ranging from about 63% to 98%. Although direct evidence for its effect on Zika is still being gathered, these results provide a strong basis for its potential to prevent Zika infection. Participants in this trial will receive the TetraVax-DV-TV003 vaccine to evaluate its effectiveness against Zika, while others will receive PlasmaLyte as a control. ^{1 2 4 5 6}

Who Is on the Research Team?

Anna Durbin, M.D.

Principal Investigator

Johns Hopkins Bloomberg School of Public Health

Are You a Good Fit for This Trial?

This trial is for individuals who have had Zika virus (ZIKV) before or those who haven't but received the TV003 dengue vaccine. It aims to understand if previous infection or vaccination can protect against a new ZIKV strain. Specific eligibility criteria are not provided.

Inclusion Criteria

Must be able to complete the informed consent process and comprehension assessment independently and without assistance

Good general health as determined by physical examination, laboratory screening, and review of medical history

I agree to use barrier methods during sex for 90 days after the Zika virus study starts.

Exclusion Criteria

Hepatitis C virus (HCV) infection, by screening and confirmatory assays

Evidence of recent opiate use based on urine toxicology screen

Hepatitis B virus (HBV) infection, by Hepatitis B surface antigen (HBsAg) screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 8 weeks

Treatment

Participants receive the TV003 dengue vaccine or PlasmaLyte, followed by a ZIKV challenge

6 months

Multiple visits for vaccination and monitoring

Challenge and Follow-up

Participants are challenged with ZIKV and monitored for safety and effectiveness

26 weeks

Regular follow-up visits for monitoring

Long-term Follow-up

Participants are monitored for long-term safety and immune response

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TetraVax-DV-TV003

Trial Overview

The study tests whether prior ZIKV infection or immunization with the TV003 dengue vaccine prevents reinfection when exposed to a different ZIKV strain, known as ZIKV-SJRP/2016-184. Participants will be exposed to this challenge virus.

How Is the Trial Designed?

Group I: Arm 2: Subjects with previous ZIKV infection Experimental Treatment 1 Intervention

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

Group II: Arm 1: DENV/ZIKV naive subjects receiving TV003 Experimental Treatment 2 Interventions

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

Group III: Infectivity Controls: DENV/ZIKV naive subjects receiving PlasmaLyte Placebo Group 2 Interventions

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

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Johns Hopkins Bloomberg School of Public Health

Collaborator

Trials

441

Recruited

2,157,000+

Published Research Related to This Trial

The live attenuated tetravalent dengue vaccine candidate (TV003) was well tolerated in a study of 58 individuals with prior flavivirus exposure, showing only mild adverse events, primarily rash.

After one dose of TV003, 87% of participants developed a strong immune response with neutralizing antibodies against all four dengue serotypes, indicating that a single dose may be sufficient for protection against dengue disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In a randomized trial, the live attenuated tetravalent dengue vaccine TV003 is well-tolerated and highly immunogenic in subjects with flavivirus exposure prior to vaccination. Whitehead, SS., Durbin, AP., Pierce, KK., et al.[2018]

Dengvaxia (CYD-TDV) is the first dengue vaccine approved by the US FDA, showing efficacy in preventing severe secondary dengue infections, particularly in individuals with prior dengue exposure.

The review highlights that the vaccine's effectiveness varies based on seroprevalence, serotypes, and age, suggesting that it can be integrated into global vaccination strategies to combat dengue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dengvaxia: the world's first vaccine for prevention of secondary dengue. Tully, D., Griffiths, CL.[2021]

The tetravalent dengue vaccine (TDV) developed by Sanofi Pasteur was found to be safe, with no serious adverse events reported among the 66 healthy adult participants in the study.

The vaccine demonstrated strong immunogenicity, as all participants who received three doses achieved seroconversion against all four dengue virus serotypes, indicating effective immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel tetravalent dengue vaccine is well tolerated and immunogenic against all 4 serotypes in flavivirus-naive adults. Morrison, D., Legg, TJ., Billings, CW., et al.[2010]

The tetravalent dengue vaccine (TDV) was found to be well tolerated among 360 healthy volunteers aged 1.5 to 45 years, with only mild adverse events like injection site pain and itching reported more frequently than with placebo.

TDV demonstrated strong immunogenicity, achieving over 95% seropositivity for dengue serotypes 1-3 and between 72.7% to 100% for serotype 4 after two doses, indicating its potential effectiveness in providing immunity against dengue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Immunogenicity of a Tetravalent Dengue Vaccine Candidate in Healthy Children and Adults in Dengue-Endemic Regions: A Randomized, Placebo-Controlled Phase 2 Study. Sirivichayakul, C., Barranco-Santana, EA., Esquilin-Rivera, I., et al.[2016]

TAK-003, a dengue tetravalent vaccine, has shown a good safety profile in a large study involving 14,627 participants aged 4-60, with fewer serious adverse events compared to the placebo group (6% vs 8%).

The vaccine was well tolerated across different age groups, with mild injection site reactions being the most common side effects, and no significant safety risks were identified, making it a promising option for dengue prevention regardless of previous exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Safety Experience of TAK-003 for Dengue Fever: A New Tetravalent Live Attenuated Vaccine Candidate. Patel, SS., Rauscher, M., Kudela, M., et al.[2023]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06805487

Evaluation of the Protective Efficacy of TV003 or Previous ...

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 ...

2.

withpower.com

withpower.com/trial/tetravax-dv-tv003-for-zika-virus-c868f

TetraVax-DV-TV003 for Zika Virus

The vaccine demonstrated strong immunogenicity, as all participants who received three doses achieved seroconversion against all four dengue virus serotypes, ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8907379/

Current Development and Challenges of Tetravalent Live ...

The efficacy varied among the serotypes, with reported efficacies of 73.7%, 97.7%, 62.6% against DENV1, DENV2, and DENV3 respectively (62). The results for ...

4.

synapse.patsnap.com

synapse.patsnap.com/drug/4fb79e34aa434bb2a9b94cc39e884289

TetraVax-DV-TV003(Instituto Butantan) - Drug Targets ...

Vaccine efficacy was 80.1% (95% CI, 66.0 to 88.4) among participants 2 to 6 years of age, 77.8% (95% CI, 55.6 to 89.6) among those 7 to 17 years of age, and ...

5.

thelancet.com

thelancet.com/journals/langlo/article/PIIS2214-109X(23)00522-3/fulltext

Long-term efficacy and safety of a tetravalent dengue ...

2-year follow-up data from an ongoing phase 3 trial (NCT02406729) of a single dose of TV003/Butantan-DV showed 79·6% overall efficacy against dengue disease in ...

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S1201971219300402

Dengue vaccine development: Global and Indian scenarios

Data at hand from the TetraVax-DV phase I trials as well as upcoming data from the ongoing phase II and phase III trials of the NIH vaccine in the Asian ...