PXVX0317 Booster for Chikungunya

Not currently recruiting at 23 trial locations

Overseen By Michael P Zimmerman, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Bavarian Nordic

Must not be taking: Immunosuppressants, Immunomodulators

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

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 booster for a vaccine targeting chikungunya, a mosquito-borne virus that causes joint pain and fever. The goal is to assess the safety and effectiveness of the booster several years after the initial vaccination. Participants will receive either the booster (PXVX0317) or a placebo (a harmless substance with no active ingredients) for comparison. This trial includes adults and teens who previously received the chikungunya vaccine in an earlier study and are generally healthy. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are using systemic immunomodulatory or immunosuppressive medications, you may not be eligible to participate. It's best to discuss your specific medications with the study team.

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

Research has shown that PXVX0317, also known as the CHIKV VLP vaccine, is generally safe. One study found that the vaccine typically causes only mild side effects, such as soreness at the injection site or a mild fever, similar to other common vaccines. Another study showed that most recipients did not experience serious side effects. The advanced stage of this trial indicates that the vaccine has already passed earlier safety tests in humans, providing strong evidence of its safety for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard of care for chikungunya, which primarily focuses on managing symptoms with pain relievers and anti-inflammatory drugs, PXVX0317 offers a more targeted approach. This investigational treatment is a virus-like particle (VLP) vaccine booster designed to enhance immunity against the chikungunya virus, even years after an initial vaccination. Researchers are excited about PXVX0317 because it could provide long-lasting protection against the virus, potentially reducing the need for ongoing symptom management and offering a proactive strategy to prevent the disease.

What evidence suggests that this trial's treatments could be effective for Chikungunya?

Research has shown that the PXVX0317 Chikungunya vaccine, also known as the CHIKV VLP vaccine, appears promising. Studies have found that this vaccine can generate a strong immune response in most people within two weeks of administration. Data indicates that a single dose effectively helps participants produce antibodies, proteins that combat the virus. Early findings suggest that the vaccine's protection lasts for at least six months. In this trial, participants will receive either the PXVX0317 booster or a placebo booster at different intervals after the initial vaccination. This evidence supports the idea that the PXVX0317 booster could effectively enhance the body's defense against the Chikungunya virus over the long term. ^{4 5 6 7 8}

Who Is on the Research Team?

Patrick Ajiboye, MD

Principal Investigator

Bavarian Nordic

Are You a Good Fit for This Trial?

Adults and adolescents aged 12 to under 65 who previously received the PXVX0317 vaccine in an earlier study, are generally healthy, and have complied with previous study protocols. Women of childbearing potential must use effective contraception from a month before until six months after receiving the booster.

Inclusion Criteria

I received a dose of the PXVX0317 vaccine in a previous study.

I am between 12 and 64 years old.

Participant voluntarily signed and agreed to be contacted for potential screening and enrollment in a future study

Exclusion Criteria

History of severe allergic reaction or anaphylaxis to any component of the investigational product

My condition is not listed in the exclusion criteria of the related study.

Measurable anti-CHIKV SNA at Day 1 in the feeder study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Booster Vaccination

Participants receive a CHIKV VLP vaccine booster at 3, 4, or 5 years post-initial vaccination

1 day

1 visit (in-person)

Short-term Follow-up

Participants are monitored for safety and immunogenicity 21 days after booster vaccination

3 weeks

1 visit (in-person)

Long-term Follow-up

Participants are monitored for safety and immunogenicity at yearly intervals up to 5 years post-initial vaccination

5 years

What Are the Treatments Tested in This Trial?

Interventions

• PXVX0317

Trial Overview This phase 3 trial is testing the long-term safety and immune response to a booster dose of PXVX0317 vaccine for Chikungunya fever. Participants will be randomly assigned to receive either the booster or a placebo, in a double-blind setup where neither they nor the researchers know which one they're getting.

How Is the Trial Designed?

Group I: Group 3a Active Control 1 Intervention

CHIKV VLP vaccine booster, 5 years post initial vaccination

Group II: Group 1a Active Control 1 Intervention

CHIKV VLP vaccine booster, 3 years post initial vaccination

Group III: Group 2a Active Control 1 Intervention

CHIKV VLP vaccine booster, 4 years post initial vaccination

Group IV: Group 4 Active Control 1 Intervention

Unrandomized or unboosted participants, for any reason

Group V: Group 3b Placebo Group 1 Intervention

Placebo booster, 5 years post initial vaccination

Group VI: Group 1b Placebo Group 1 Intervention

Placebo booster, 3 years post initial vaccination

Group VII: Group 2b Placebo Group 1 Intervention

Placebo booster, 4 years post initial vaccination

Who Is Running the Clinical Trial?

Bavarian Nordic

Lead Sponsor

Trials

67

Recruited

50,900+

Paul Chaplin

Bavarian Nordic

Chief Executive Officer since 2014

PhD in Immunology from Bristol University

Jean-Christophe May

Bavarian Nordic

Chief Medical Officer since 2020

PharmD and MBA

Published Research Related to This Trial

The PXVX0317 vaccine, an aluminium hydroxide-adjuvanted formulation, was found to be safe and well-tolerated, with no serious adverse events reported, and it induced a strong immune response against the Chikungunya virus lasting up to 2 years.

Participants receiving a booster dose of the vaccine showed a significant increase in neutralizing antibody levels, highlighting the potential for enhanced immunity with additional doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted chikungunya virus-like particle vaccine: a randomised, double-blind, parallel-group, phase 2 trial. Bennett, SR., McCarty, JM., Ramanathan, R., et al.[2022]

The PXVX0317 vaccine induced strong and lasting neutralizing antibody responses against the chikungunya virus (CHIKV) in humans, with effects observed up to 6 months post-immunization, based on a phase 2 clinical trial.

Monoclonal antibodies derived from vaccinated individuals showed potent neutralization of CHIKV and related viruses, highlighting the vaccine's potential to provide broad protection against multiple alphaviruses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A chikungunya virus-like particle vaccine induces broadly neutralizing and protective antibodies against alphaviruses in humans. Raju, S., Adams, LJ., Earnest, JT., et al.[2023]

The study developed a novel CHIKV reporter virus (CHIKV-iRFP) that maintains the same replication and virulence as the original virus, making it a valuable tool for studying chikungunya virus dynamics.

CHIKV-iRFP demonstrated efficient replication and spread in susceptible mouse models, particularly showing a strong preference for bone marrow, which can help in evaluating the effectiveness of potential vaccines and antiviral treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Visualization of chikungunya virus infection in vitro and in vivo. Zhang, HL., Dong, HL., Zhang, YN., et al.[2020]

Researchers have developed chikungunya virus (CHIKV) vaccine candidates using recombinant baculovirus technology, which allows for large-scale production in insect cells.

These vaccine candidates, especially the virus-like particles (VLPs), have demonstrated strong immune responses and protection against CHIKV in various animal models, indicating their potential efficacy for human use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Production of Chikungunya Virus-Like Particles and Subunit Vaccines in Insect Cells. Metz, SW., Pijlman, GP.[2018]

A phase 1 study of a chikungunya virus (CHIKV) vaccine showed that it elicited neutralizing antibody responses against 9 viral strains from all 3 CHIKV genotypes, indicating potential cross-protection.

The minimal differences in antibody responses among the genotypes suggest that a vaccine based on a single CHIKV strain could effectively protect against all three genotypes, which is promising given the lack of licensed vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Virus-Like Particle Vaccine Elicits Broad Neutralizing Antibody Responses in Humans to All Chikungunya Virus Genotypes. Goo, L., Dowd, KA., Lin, TY., et al.[2018]

In a phase 2 study involving 400 participants, the CHIKV VLP vaccine was found to be well-tolerated, with only a higher incidence of injection site swelling in seropositive recipients (10.3%) compared to seronegative recipients (0.6%).

The vaccine elicited stronger immune responses in seropositive individuals, with higher neutralizing antibody levels persisting for 72 weeks, indicating that pre-existing immunity may enhance the vaccine's immunogenicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chikungunya virus virus-like particle vaccine is well tolerated and immunogenic in chikungunya seropositive individuals. McCarty, JM., Bedell, L., Mendy, J., et al.[2023]

A chikungunya virus (CHIKV) vaccine candidate based on virus-like particles (VLP) is in late-stage clinical testing and shows promising safety and immunogenicity results from both nonclinical and clinical studies.

The effectiveness of the CHIKV VLP vaccine can be influenced by variations in its coding sequence and the expression platform used, which affect how well the vaccine produces immune responses and protects against the virus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunological implications of diverse production approaches for Chikungunya virus-like particle vaccines. Thompson, D., Metz, SW., Abad, C., et al.[2022]

Vaccination with CHIKV virus-like particles (VLPs) provided complete protection against lethal CHIKV challenge in mice, demonstrating their efficacy as a potential vaccine candidate.

In contrast, subunit vaccines targeting individual CHIKV glycoproteins (E1 and E2) offered only partial protection, highlighting that VLPs elicit a stronger immune response and higher neutralizing antibody levels, which are crucial for protection against the virus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chikungunya virus-like particles are more immunogenic in a lethal AG129 mouse model compared to glycoprotein E1 or E2 subunits. Metz, SW., Martina, BE., van den Doel, P., et al.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11530495/

Chikungunya Virus Vaccines: A Review of IXCHIQ and ... In this review, we summarize published data from pre-clinical and clinical trials for the IXCHIQ and PXVX0317 vaccines.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03483961

Trial of a Chikungunya Vaccine, PXVX0317 CHIKV-VLP, in ... The goal of this Phase 2 trial is to evaluate the immune response to and safety profile of various doses/formulations/and schedules of administration of ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1473309922002262

Safety and immunogenicity of PXVX0317, an aluminium ... Our data show that a single adjuvanted 40 μg dose of PXVX0317 was highly immunogenic; all evaluable participants were seropositive within 28 days of the ...

4. cdc.gov cdc.gov/acip/downloads/slides-2024-10-23-24/03-Chikungunya-Jenkins-508.pdf

CHIKV VLP vaccine 1 Demographic characteristics of the IEP are displayed. 2 Percentages are based on the number of participants in each study arm. BMI, body mass ...

5. medrxiv.org medrxiv.org/content/10.1101/2024.10.10.24315205v2.full-text

Chikungunya Virus VLP Vaccine: Phase 3 Trial in Adults ... CHIKV VLP vaccine induces a rapid and robust immune response in most individuals by 14 days postvaccination, with protection lasting through 6- ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40158526/

Chikungunya virus virus-like particle vaccine safety and ... Here, we report safety, tolerability, and immunogenicity data for Vimkunya versus placebo in healthy adolescents and adults aged 12-64 years ...

7. thelancet.com thelancet.com/journals/lanmic/article/PIIS2666-5247(24)00268-4/fulltext

Safety and immunogenicity of an adjuvanted chikungunya ... These data suggest that a single adjuvanted 40 μg dose of CHIKV VLP vaccine is well tolerated and immunogenic in previous recipients of ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05072080

Study Details | NCT05072080 | A Phase 3 Trial of the VLP ... To evaluate the safety of PXVX0317 (CHIKV VLP vaccine) in healthy adult and adolescent participants 12 to <65 years of age. To compare the anti-CHIKV serum ...