Investigational Yellow Fever Vaccine vs Standard Vaccine for Yellow Fever

(VYF02 Trial)

Not currently recruiting at 34 trial locations

Overseen By Trial Transparency email recommended (Toll free number for US & Canada)

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Sanofi Pasteur, a Sanofi Company

Must not be taking: Immunosuppressants, Antivirals

Disqualifiers: Immunodeficiency, Flavivirus, Hepatitis B/C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new yellow fever vaccine, produced on serum-free Vero cells, to determine its efficacy compared to the standard vaccine. Researchers aim to assess how well people's bodies respond to the new vaccine and ensure its safety. The trial includes two groups: one receiving the new vaccine and the other the standard one. It suits adults who have never received a yellow fever vaccine or had a flavivirus infection and who do not have immune system issues or allergies to vaccine components. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy, long-term corticosteroids, or have taken any anti-viral medications recently, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the new yellow fever vaccine (vYF), developed using Vero cells without serum, is promising in terms of safety. Earlier studies found that the vaccine is safe and generally well-tolerated when administered as an injection. It has a similar safety profile and immune response to the yellow fever vaccines already approved for use.

The trial is currently in Phase 2, the middle stage of testing. Researchers have gathered some initial safety data from smaller trials, though it is not as comprehensive as data from later stages. However, no major safety issues have been reported so far, which is encouraging for potential participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

The investigational yellow fever vaccine is unique because it's produced on serum-free Vero cells, unlike the traditional yellow fever vaccines like YF-VAX. This serum-free production method aims to improve safety and reduce the risk of allergic reactions associated with animal-derived components. Researchers are excited about this treatment because it has the potential to provide a safer vaccination option without compromising effectiveness.

What evidence suggests that this trial's vaccines could be effective for yellow fever?

This trial will compare the investigational yellow fever vaccine (vYF), made without serum, with the standard vaccine, YF-VAX. Research has shown that vYF works as well as currently available vaccines. Studies have found that it triggers the body to produce an immune response, indicating its effectiveness. In earlier trials, vYF provided strong protection against yellow fever, even completely preventing it in some cases. The vaccine has been safe, showing no major differences compared to existing vaccines. This suggests that vYF could protect against yellow fever as effectively as current vaccines. ^{1 3 6 7 8}

Who Is on the Research Team?

Clinical Sciences & Operations

Principal Investigator

Sanofi Pasteur, a Sanofi Company

Are You a Good Fit for This Trial?

Adults aged 18-60 in the USA who've never had yellow fever or a vaccine against it can join. Women must not be pregnant/breastfeeding, use contraception, and have negative pregnancy tests before/during the study. Participants should be free of certain infections, immune conditions, and not taking specific medications.

Inclusion Criteria

I am not able to have children because I am postmenopausal for over a year or have been surgically sterilized.

Informed consent form has been signed and dated.

You are of childbearing potential and agree to use an effective contraceptive method or abstinence from at least 4 weeks prior to vaccination until at least 4 weeks after vaccination

Exclusion Criteria

I or someone in my family has had issues with the thymus.

Known systemic hypersensitivity to any of the vaccine components, eggs, or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances.

I haven't had vaccines 4 weeks before or plan to within 4 weeks after the study vaccine, except for flu shots.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination

Participants receive one injection of either vYF or YF-VAX on Day 1

1 day

1 visit (in-person)

Immediate Observation

Participants are monitored for immediate adverse events for 30 minutes post-vaccination

30 minutes

1 visit (in-person)

Short-term Follow-up

Participants are monitored for solicited and unsolicited adverse events and seroconversion up to 6 months

6 months

Long-term Follow-up

Participants are monitored for related serious adverse events and seroconversion annually up to 5 years

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Yellow fever vaccine (produced on serum-free Vero cells)

Trial Overview The trial is testing a new yellow fever vaccine made with Vero cells against the standard YF-VAX. It measures if people's bodies respond similarly to both vaccines by looking at antibodies after 28 days and monitors safety over time.

How Is the Trial Designed?

Group I: vYF Experimental Treatment 1 Intervention

1 injection of vYF at Day 1

Group II: YF-VAX Active Control 1 Intervention

1 injection of YF-VAX at Day 1

Who Is Running the Clinical Trial?

Sanofi Pasteur, a Sanofi Company

Lead Sponsor

Trials

429

Recruited

6,140,000+

Paul Hudson

Sanofi Pasteur, a Sanofi Company

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Dr. Thomas Triomphe

Sanofi Pasteur, a Sanofi Company

Chief Medical Officer since 2020

MD from Tehran University of Medical Sciences

Published Research Related to This Trial

Two fatal cases of hemorrhagic fever were reported in Brazil following the yellow fever 17DD vaccine, highlighting a rare but serious complication associated with this vaccine.

The cases involved a 5-year-old girl and a 22-year-old woman, both of whom exhibited severe symptoms and died shortly after vaccination, suggesting that individual host factors may play a role in these adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious adverse events associated with yellow fever 17DD vaccine in Brazil: a report of two cases. Vasconcelos, PF., Luna, EJ., Galler, R., et al.[2019]

The yellow fever vaccine (YFV) was found to be safe and well tolerated in HIV-infected patients with high CD4 T-cell counts, showing that it can be administered without significant risk, as evidenced by a study involving 40 HIV+ individuals and 31 HIV- individuals.

While both groups developed protective antibody levels after vaccination, HIV+ patients exhibited a lower T-cell response compared to HIV- participants, indicating that while the vaccine is effective, the immune response may be less robust in those with HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of yellow fever vaccine in HIV-1-infected patients. Colin de Verdiere, N., Durier, C., Samri, A., et al.[2019]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1473309924004067

Safety and immunogenicity of a next-generation live ... A next-generation live-attenuated yellow fever vaccine candidate (vYF), produced in a Vero cell line has shown similar immunogenicity to licensed yellow fever ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11424963/

observations from a phase I randomised clinical trial - PMC Safety and immunogenicity of a next-generation live-attenuated yellow fever vaccine produced in a Vero cell line in the USA: a phase 1 ...

3. nature.com nature.com/articles/s41541-022-00595-6

A phase I clinical study to assess safety and ... This was a Phase 1, randomized controlled study on the SII YFV (SC and IM) compared to STAMARIL® in 60 adults. The vaccine was found highly ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39153488/

a phase 1 randomised, observer-blind, active- ... A next-generation live-attenuated yellow fever vaccine candidate (vYF), produced in a Vero cell line has shown similar immunogenicity to licensed yellow fever ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0264410X22014645

Evaluation of safety and immuno-efficacy of a next ... Additionally, vYF provided effective resistance to virulent challenge with wild-type YFV Asibi including complete protection against YFV-induced ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31047674/

Purification of yellow fever virus produced in Vero cells for ... A new vaccine based on the production of the attenuated 17DD virus in serum-free conditions in Vero cells propagated in bioreactors, followed by chromatography ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04142086

Dose-ranging Study of an Investigational Yellow Fever ... The primary objectives of the study are: To describe the safety profile of each of the 3 dosages of vYF and of YF-VAX® within the 28 days post-vaccination ...

8. cell.com cell.com/iscience/fulltext/S2589-0042(24)02197-7

A safer cell-based yellow fever live attenuated vaccine ... In this study, we developed a new live attenuated yellow fever vaccine, YF17D-Δ77, which is safer than YF17D and exhibits equivalent ...