PXVX0317 Booster for Chikungunya

Recruiting at 23 trial locations

Overseen By Michael P Zimmerman, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: Bavarian Nordic

Must not be taking: Immunosuppressants, Immunomodulators

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

The purpose of this phase 3 multicenter, randomized, double-blind, placebo-controlled rollover study is to evaluate the safety and long-term immunogenicity of CHIKV VLP vaccine in adult and adolescent participants and to evaluate CHIKV VLP booster vaccine induced serum neutralizing antibody (SNA) response at 3, 4, or 5 years post-initial CHIKV VLP vaccination.

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.

What safety data is available for the PXVX0317 Chikungunya vaccine?

The PXVX0317 vaccine, also known as the CHIKV VLP vaccine, has been tested in humans and found to be generally well-tolerated. In a study, some participants experienced mild side effects like injection site swelling, but overall, the vaccine was considered safe. ^{1 2 3 4 5}

How is the PXVX0317 treatment for chikungunya different from other treatments?

PXVX0317 is unique because it is a vaccine made from virus-like particles (VLPs) that mimic the chikungunya virus, helping the body produce a strong immune response without causing disease. Unlike other treatments, it uses an adjuvant (a substance that enhances the body's immune response) called aluminium hydroxide, and it has shown the ability to generate antibodies that can neutralize multiple related viruses, not just chikungunya. ^{1 3 6 7 8}

Research Team

Patrick Ajiboye, MD

Principal Investigator

Bavarian Nordic

Eligibility Criteria

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.

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

Generally healthy, in the opinion of the investigator, based on medical history and physical examination

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

Trial Timeline

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

Treatment Details

Interventions

• PXVX0317 (Cancer Vaccine)

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Chikungunya virus virus-like particle vaccine is well tolerated and immunogenic in chikungunya seropositive individuals. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

A chikungunya virus-like particle vaccine induces broadly neutralizing and protective antibodies against alphaviruses in humans. [2023]

4. Netherlands 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. [2013]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Immunological implications of diverse production approaches for Chikungunya virus-like particle vaccines. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Production of Chikungunya Virus-Like Particles and Subunit Vaccines in Insect Cells. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

A Virus-Like Particle Vaccine Elicits Broad Neutralizing Antibody Responses in Humans to All Chikungunya Virus Genotypes. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Visualization of chikungunya virus infection in vitro and in vivo. [2020]