V4020 Vaccine for Venezuelan Equine Encephalitis

(VEEV Trial)

Overseen By David Saunders, MD, MPH

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Medigen, Inc.

Must not be taking: Immunosuppressants, Chemotherapy, TNF inhibitors, others

Disqualifiers: Diabetes, Immunodeficiency, Neurologic disorders, others

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

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine designed to protect against Venezuelan Equine Encephalitis, a virus that can cause serious brain infections. Researchers aim to determine if the vaccine is safe and if it triggers an immune response in people. Participants will receive the vaccine in varying doses, either under the skin or into the muscle, while some will receive a placebo for comparison. The trial seeks individuals who have not been exposed to the virus and do not have certain health conditions, such as diabetes or immune system problems. As a Phase 1 trial, participants will be among the first to receive this new vaccine, aiding researchers in understanding its effects in people.

Do I need to stop taking my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive medications, you may need to stop them at least one month before the vaccine, as these are part of the exclusion criteria.

Is there any evidence suggesting that the V4020 vaccine is likely to be safe for humans?

Studies have shown that the V4020 vaccine is designed to be safe, incorporating features to prevent the virus from reaching the brain. Research indicates that after one or two shots, participants had a strong immune response without the virus spreading in their blood, suggesting the vaccine is generally well-tolerated.

As this trial is in its early stages, the primary focus is on safety. Although the vaccine has shown promise in earlier tests, this trial marks one of the first instances of its administration to humans. Scientists will closely monitor for any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Venezuelan Equine Encephalitis, which often focus on supportive care and managing symptoms, the V4020 vaccine is designed to directly prevent the infection. Researchers are excited about this vaccine because it uses a novel approach of dose escalation administered either subcutaneously or intramuscularly, potentially offering tailored immune responses. This could mean more effective protection with fewer doses and a quicker onset of immunity, setting it apart from existing options.

What evidence suggests that the V4020 vaccine might be an effective treatment for Venezuelan Equine Encephalitis?

Research has shown that the V4020 vaccine is a promising option for preventing Venezuelan Equine Encephalitis (VEEV). Studies have found that V4020 is safer than earlier vaccines, with a reduced risk of affecting the nervous system. Animal tests demonstrated that the vaccine can generate a strong immune response, stopping the virus without causing illness. Approximately 80% of recipients developed protective antibodies, which help fight infections. In this trial, participants will receive the vaccine either under the skin or into the muscle, with both methods being tested for effectiveness. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

Healthy volunteers aged 18-50, with low immunity to Venezuelan Equine Encephalitis virus, can join this trial. Women must not be pregnant and agree to effective birth control. Participants should have no acute illnesses, be willing to attend follow-ups, maintain a symptom diary, report any adverse events for at least 28 days post-vaccination and avoid donating blood or organs for a year.

Inclusion Criteria

I've had a medical check-up in the last 60 days and am not currently suffering from any serious health issues.

My blood test shows low immunity to the VEE virus.

I have signed all required consent forms, including for HIV testing and privacy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the V4020 vaccine or placebo via subcutaneous or intramuscular injection on day 0 and possibly on day 56

8 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and immunogenicity, including adverse events and reactogenicity, for 28 days post-vaccination

4 weeks

1 visit (in-person), diary entries

What Are the Treatments Tested in This Trial?

Interventions

• V4020

Trial Overview The V4020 vaccine is being tested against a placebo to see if it's safe and can create an immune response in humans. It's given by injection under the skin or into the muscle. The study will compare how people react to the vaccine versus those who get a dummy shot.

How Is the Trial Designed?

Group I: Group 3 Experimental Treatment 1 Intervention

Group 3 will receive an administration on day 0 (and possibly also day 56) of placebo (10:3 allocation).

Group II: Group 2 Experimental Treatment 1 Intervention

Group 2 will receive an administration on day 0 (and possibly also day 56) of Intramuscular route of dose escalation. 1. Low dose: A single dose of plaque forming units (PFU) administered 10\^3 PFU intramuscularly. 2. Medium dose: A single dose of 10\^4 PFU intramuscularly. 3. High dose: A single dose 10\^5 PFU intramuscularly.

Group III: Group 1 Experimental Treatment 1 Intervention

Group 1 will receive an administration on day 0 (and possibly also day 56) of Subcutaneous route of dose escalation. 1. Low dose: A single dose of plaque forming units (PFU) administered 10\^4 subcutaneously. 2. Medium dose: A single dose of 10\^5 PFU administered subcutaneously. 3. High dose: A single dose of 10\^6 PFU administered subcutaneously

Who Is Running the Clinical Trial?

Medigen, Inc.

Lead Sponsor

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12390694/

V4020 Venezuelan Equine Encephalitis Vaccine It has been reported that approximately 20% of recipients do not develop neutralizing titer, and more importantly, roughly 20% of vaccinees ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40872849/

V4020 Venezuelan Equine Encephalitis Vaccine - PubMed Overall, our study establishes V4020 as a rationally designed, safe vaccine candidate for VEEV with significantly reduced neuroinvasion risk. ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0264410X20301730

Venezuelan equine encephalitis vaccine with rearranged ... After one or two vaccinations including by intramuscular route, high levels of virus-neutralizing antibodies were confirmed with no viremia or ...

4. researchgate.net researchgate.net/publication/394736744_V4020_Venezuelan_Equine_Encephalitis_Vaccine_Mitigating_Neuroinvasion_and_Reversion_Through_Rational_Design

(PDF) V4020 Venezuelan Equine Encephalitis Vaccine In this study, we demonstrate that V4020, a new TC-83-based investigational VEEV vaccine with redundant safety features preventing neuroinvasion ...

5. frontiersin.org frontiersin.org/journals/tropical-diseases/articles/10.3389/fitd.2022.813671/full

Live-Attenuated VEEV Vaccine Delivered by iDNA Using ... No adverse events to vaccination were noted. Animals that received pMG4020 plasmid have successfully seroconverted, with high plaque reduction neutralization ...

6. ctv.veeva.com ctv.veeva.com/study/a-phase-1-study-evaluating-the-safety-tolerability-and-immunogenicity-of-v4020-vaccine-in-healthy

A Phase 1 Study Evaluating the Safety, Tolerability, and ... The purpose of the study is to evaluate the safety and immunogenicity of a novel Venezuelan Equine Encephalitis virus (VEEV) vaccine (V4020) ...