Norovirus Vaccine for Norovirus

Overseen By Nick D'Amato

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Vaxart

Must not be taking: Antibiotics, Antacids, Corticosteroids, others

Disqualifiers: Cancer, Diabetes, HIV, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to stop using certain medications before and during the study. You must avoid antibiotics, proton pump inhibitors, H2 blockers, antacids, and nonsteroidal anti-inflammatory drugs for 7 days before and during the study. Medications affecting immune function must be stopped 14 days before and during the study, except for certain allergen immunotherapies.

What evidence supports the effectiveness of the norovirus vaccine treatment VXA-G1.1-NN, VXA G1.1 NN-T, VXA-G2.4-NS, VXA G2.4 NS-T?

Research shows that a similar approach using a recombinant adenovirus expressing the norovirus capsid protein in mice led to strong immune responses, suggesting that this strategy could be effective for norovirus vaccines. ^{1 2 3 4 5}

Is the Norovirus vaccine safe for humans?

The Norovirus vaccine has been tested in healthy adults and shown to be generally safe. In a study, most participants experienced mild symptoms like local irritation at the injection site, which resolved over time. Severe adverse events were rare, and the vaccine was well-tolerated at different dose levels. ^{2 6 7 8 9}

How does the norovirus vaccine treatment VXA-G1.1-NN differ from other treatments for norovirus?

The VXA-G1.1-NN treatment is unique because it uses a dry powder formulation for intranasal delivery, which simplifies administration and targets both systemic and mucosal immune responses without needing an additional immune booster (adjuvant). This approach is novel compared to traditional vaccines that often require injections and adjuvants to enhance immune response. ^{1 10 11 12 13}

What is the purpose of this trial?

The primary objective of this study is to determine the safety and immunogenicity of low and high dose regimens of a next generation norovirus bivalent G1.1 and G2.4 vaccine candidate in healthy participants.

Eligibility Criteria

This trial is for healthy individuals aged 18 to 80 years old who are interested in participating in a study for a new norovirus vaccine. Specific eligibility criteria details were not provided, so it's important to contact the study organizers for more information.

Inclusion Criteria

Body mass index (BMI) between 17.0 and 35.0 kg/m^2

Willing to complete all Protocol-defined procedures and assessments

I understand the study and can sign the consent form.

Exclusion Criteria

I have a stomach or intestine condition that may affect vaccine safety.

History of angioedema or serious reactions to vaccination

Positive tests for HIV, hepatitis B, or hepatitis C

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single oral dose of either low or high dose regimens of the norovirus bivalent G1.1 and G2.4 vaccine

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and immunogenicity after receiving the vaccine

4 weeks

Treatment Details

Interventions

• VXA-G1.1-NN
• VXA G1.1 NN-T
• VXA-G2.4-NS
• VXA G2.4 NS-T

Trial Overview The trial is testing different doses of two experimental norovirus vaccines: VXA-G1.1-NN and VXA-G2.4-NS, which target the G1.1 and G2.4 strains respectively. The goal is to see how safe they are and how well they can stimulate an immune response.

Participant Groups

Group I: Bivalent Low Dose Next Generation Vaccine Experimental Treatment 2 Interventions

Healthy participants will receive Norovirus GI.1 Norwalk VP1 Vaccine, Modified Oral E1-/E3-Deleted Replication Defective Recombinant Adenovirus 5 with dsRNA Adjuvant (VXA-G1.1-NN-T) (1x10\^10 infectious units (IU)) and Norovirus GII.4 Sydney VP1 Vaccine, Modified Oral E1-/E3-Deleted Replication Defective Recombinant Adenovirus 5 with dsRNA Adjuvant (VXA-G2.4-NS-T) (1x10\^10 IU) orally.

Group II: Bivalent High Dose Next Generation Vaccine Experimental Treatment 2 Interventions

Healthy participants will receive VXA-G1.1-NN-T (1x10\^11 IU) and VXA-G2.4-NS-T (1x10\^11 IU) orally. A sentinel group will be enrolled, if there is positive recommendation from the safety monitoring committee, enrollment will continue in this arm.

Group III: Bivalent High Dose Legacy Vaccine Experimental Treatment 2 Interventions

Healthy participants will receive Norovirus GI.1 Norwalk Vaccine Protein 1 (VP1) Vaccine, Oral E1-/E3-Deleted Replication Defective Recombinant Adenovirus 5 with double-stranded ribonucleic acid (dsRNA) Adjuvant (VXA-G1.1-NN) (1x10\^11 IU) and Norovirus GII.4 Sydney VP1 Vaccine, Oral E1-/E3-Deleted Replication Defective Recombinant Adenovirus 5 with dsRNA Adjuvant (VXA-G2.4-NS) (1x10\^11 IU) orally.

Who Is Running the Clinical Trial?

Vaxart

Lead Sponsor

Trials

22

Recruited

11,400+

Findings from Research

The NVX-CoV2373 vaccine, evaluated in over 31,000 participants across five clinical studies, demonstrated high efficacy against COVID-19 and a well-tolerated safety profile, with common side effects including injection site pain and fatigue.

A booster dose administered six months after the initial two doses significantly increased antibody levels against COVID-19 variants, reinforcing the vaccine's effectiveness and supporting its use in both primary and booster vaccination regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for the Novavax COVID-19 Vaccine (NVX-CoV2373), a recombinant spike protein vaccine with Matrix-M adjuvant to prevent disease caused by SARS-CoV-2 viruses. Wilkinson, B., Patel, KS., Smith, K., et al.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Intranasal administration of a recombinant adenovirus expressing the norovirus capsid protein stimulates specific humoral, mucosal, and cellular immune responses in mice. [2008]

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

Safety and Immunogenicity of Different Formulations of Norovirus Vaccine Candidate in Healthy Adults: A Randomized, Controlled, Double-Blind Clinical Trial. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

A recombinant adenovirus prime-virus-like particle boost regimen elicits effective and specific immunities against norovirus in mice. [2009]

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

Broad blockade antibody responses in human volunteers after immunization with a multivalent norovirus VLP candidate vaccine: immunological analyses from a phase I clinical trial. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Norovirus Vaccines: Current Clinical Development and Challenges. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity studies in animal models support clinical development of a bivalent norovirus-like particle vaccine produced in plants. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled, dose-escalating phase I trial to evaluate safety and immunogenicity of a plant-produced, bivalent, recombinant norovirus-like particle vaccine. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for the Novavax COVID-19 Vaccine (NVX-CoV2373), a recombinant spike protein vaccine with Matrix-M adjuvant to prevent disease caused by SARS-CoV-2 viruses. [2023]

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

Rapid Responses to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: A Randomized Controlled Trial. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Preclinical dose-ranging studies of a novel dry powder norovirus vaccine formulation. [2018]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Immunogenicity and specificity of norovirus Consensus GII.4 virus-like particles in monovalent and bivalent vaccine formulations. [2021]

12. Switzerland pubmed.ncbi.nlm.nih.gov

6-Valent Virus-Like Particle-Based Vaccine Induced Potent and Sustained Immunity Against Noroviruses in Mice. [2022]

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

Immunogenicity of Newcastle disease virus vectors expressing Norwalk virus capsid protein in the presence or absence of VP2 protein. [2022]