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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine to protect against norovirus, a virus that inflames the stomach and intestines, causing symptoms like diarrhea and vomiting. Researchers aim to determine the vaccine's safety and its effectiveness in building immunity by comparing different doses. Healthy individuals without significant medical issues or digestive conditions, who can swallow small tablets, might be suitable candidates. As a Phase 1 trial, participants will be among the first to receive this new vaccine, aiding researchers in understanding its effects in people.

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.

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

In earlier studies, the norovirus vaccines under testing have proven safe. The VXA-G1.1-NN-T vaccine was generally well-tolerated, with most participants experiencing only mild symptoms like diarrhea and headache. About one-third reported these symptoms. The vaccine also triggered strong immune responses, a positive sign.

Similarly, past research has shown the VXA-G2.4-NS-T vaccine to be safe and well-tolerated. It also helped protect against norovirus, which causes vomiting and diarrhea. The vaccine reduced the amount of virus in the body, crucial for stopping the spread of infection.

Overall, these vaccines have demonstrated safety in humans. Other studies have confirmed their safety and effectiveness in helping the body fight the virus. Prospective trial participants can feel reassured by this past safety data. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these norovirus vaccines because they use a novel delivery method: a modified oral adenovirus with a dsRNA adjuvant, which is not how traditional norovirus vaccines work. Unlike existing treatments that often focus on symptom management, these vaccines aim to prevent infection by stimulating a strong immune response against the virus. Additionally, these vaccines are designed to be taken orally, which could make them easier to administer compared to injectable vaccines. This approach could revolutionize how we prevent and control norovirus outbreaks, especially in settings where the virus spreads quickly.

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

This trial will evaluate different formulations of norovirus vaccines. Studies have shown that the VXA-G1.1-NN vaccine reduces norovirus infections, decreasing the chance of contracting the virus by 29% compared to those who did not receive the vaccine. It also reduced the amount of virus in stool and vomit, potentially helping to prevent its spread. Similarly, the VXA-G2.4-NS vaccine lowered infections by 30%. Both vaccines aim to strengthen the immune system in the gut, where norovirus typically causes issues. Overall, these vaccines have shown promising results in protecting against norovirus infections. Participants in this trial will receive either the Bivalent High Dose Next Generation Vaccine, the Bivalent Low Dose Next Generation Vaccine, or the Bivalent High Dose Legacy Vaccine. ^{3 4 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. science.org science.org/doi/10.1126/scitranslmed.adh9906

An oral norovirus vaccine generates mucosal immunity and ... VXA-G1.1-NN was safe and well tolerated, conferred protection against norovirus GI.1 challenge, and reduced viral shedding in stool and emesis.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12350415/

The Impact of Norovirus on Children and Adolescents 1 Norwalk virus VP1 gene, the observed vaccine efficacy, 29% against infection and 21% against gastroenteritis, was low. However, the 85% ...

3. cdn.who.int cdn.who.int/media/docs/default-source/immunization/pdvac/pdvac-2024/day-3/norovirus-vaccines.pdf

Norovirus Vaccine Pipeline Results also showed that the oral bivalent vaccine candidate was well tolerated, with a favorable safety profile and no vaccine-related adverse ...

4. contagionlive.com contagionlive.com/view/norovirus-vaccine-vxa-gi-1-nn-oral-vaccine-for-gastroenteritis-prevention

Oral Norovirus Gastroenteritis Vaccine VXA-GI.1-NN ... The protective efficacy for preventing NVG was 21%, while the efficacy for preventing norovirus infection was 29%. Notably, there was an 85% ...

5. cidrap.umn.edu cidrap.umn.edu/norovirus/norovirus-vaccine-produces-mucosal-immunity-phase-2b-trial

Norovirus vaccine produces mucosal immunity in phase ... 30% relative reduction in norovirus​​ Among VXA-G1. 1-NN recipients, 57.1% developed NV infection, compared with 81.5% in the placebo group, with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6124525/

Safety and immunogenicity of an oral tablet norovirus ... Diarrhea and headache were the most common solicited symptoms following VXA‑G1.1‑NN administration, both of which were reported by 15 of 23 (33%) subjects in ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03897309

NCT03897309 | Safety & Immunogenicity Study of Ad5 ... VXA-NVV-103 is a phase 1B Randomized, Double-Blind, Placebo-Controlled, Multi-Center Safety and Immunogenicity Study of Adenoviral-vector Based Oral Norovirus ...