Oral Vaccine for COVID-19

Not currently recruiting at 148 trial locations

Overseen By Nick D'Amato

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vaxart

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

Disqualifiers: Autoimmune, Immunodeficiency, Cancer, others

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

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

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 explores a new oral COVID-19 vaccine (VXA-CoV2-3.1) to assess its effectiveness in preventing symptoms compared to an existing injectable vaccine. The study focuses on a tablet form of the vaccine designed to target a recent variant of the virus. Participants should have completed their initial COVID-19 vaccinations with at least two mRNA doses and not received a COVID shot in the last six months. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications, such as antibiotics, proton pump inhibitors, H2 blockers, antacids, and nonsteroidal anti-inflammatory drugs, at least 7 days before the study and during the study. Additionally, medications that affect the immune system or gastrointestinal motility must be stopped within specific timeframes before the study. Please consult with the study team for guidance on your specific medications.

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

Research has shown that the VXA-CoV2-3.1 vaccine, which includes the XBB.1.5 strain, has been studied for safety. One study examined its use as a fifth COVID-19 vaccine dose and checked for 28 different side effects. This study did not find any major safety concerns, suggesting the vaccine is generally well-tolerated.

For the VXA-CoV2-3.3 vaccine, which targets the KP.2 strain, less direct safety data is available. However, since this trial is in a phase where safety is still being closely monitored, earlier research likely showed it was safe enough to continue testing. In this context, safety means no severe or unexpected side effects were found in earlier trials.

Overall, the available information suggests that both VXA-CoV2-3.1 and VXA-CoV2-3.3 have not shown serious safety issues in studies conducted so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the VXA-CoV2-3.1 and VXA-CoV2-3.3 treatments because they offer a novel oral vaccine approach to COVID-19 protection, which is different from the standard injectable options like COMIRNATY®. This oral tablet vaccine is potentially easier to administer and could improve vaccination rates by eliminating the need for needles. Moreover, these vaccines target specific variants, such as XBB.1.5 and KP.2, which could enhance their effectiveness against new strains of the virus. These unique features could make them a game-changer in the ongoing battle against COVID-19.

What evidence suggests that this trial's treatments could be effective for COVID-19?

In this trial, participants will receive different COVID-19 vaccines. Research has shown that vaccines targeting the XBB.1.5 variant, like VXA-CoV2-3.1, have not been very effective at preventing infections but do help reduce serious outcomes, such as hospital stays. Meanwhile, the VXA-CoV2-3.3 vaccine is another treatment option in this trial, tested for its effectiveness against newer virus strains. Current studies are examining how well it prevents COVID-19 symptoms compared to other vaccines. The results are still under review to understand its potential benefits in everyday situations. ^{1 6 7 8 9}

Who Is on the Research Team?

James Cummings, MD

Principal Investigator

Vaxart, Inc.

Are You a Good Fit for This Trial?

This trial is for adults who have already been vaccinated against COVID-19. Participants should be in good health and not currently infected with COVID-19. The full eligibility criteria are not provided, so additional requirements may apply.

Inclusion Criteria

I agree to use effective birth control before and after the study.

I have completed the COVID-19 vaccination series with 2 or more mRNA doses.

Is medically stable, as determined by the site investigator (based on review of health status, vital signs, medical history, and physical examination) with screening lab values within normal limits or abnormalities assessed as not clinically significant

Exclusion Criteria

I have not had any serious health or mental issues needing frequent treatment in the last 3 months, except well-controlled diabetes.

Any known allergies to components contained in the investigational product (including fish gelatin) or comparator or latex allergy (including polyethylene glycol [PEG] allergies) and/or history of serious reactions to vaccination such as anaphylaxis, respiratory problems, hives, or abdominal pain

I haven't taken antibiotics or stomach acid-related meds in the last 7 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the VXA-CoV2-3.1 oral vaccine or the COMIRNATY® injectable vaccine

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including the assessment of treatment-emergent adverse events

12 months

What Are the Treatments Tested in This Trial?

Interventions

• VXA-CoV2-3.1

Trial Overview The study is testing the effectiveness of a new oral vaccine tablet called VXA-CoV2-3.1 compared to an existing mRNA booster shot, COMIRNATY®, for preventing symptoms of COVID-19 in previously immunized adults.

How Is the Trial Designed?

Group I: VXA-CoV2-3.3 Experimental Treatment 1 Intervention

If no dose-related toxicities are observed, and upon the recommendation of the Data and Safety Monitoring Board following review of Day 31 safety data in the initial safety cohorts (and possibly immunogenicity data), enrollment will continue with the remaining participants who will be randomized to receive a single dose of VXA-CoV2-3.3 (KP.2 vaccine).

Group II: VXA-CoV2-3.1 Safety Sentinel Cohort Experimental Treatment 1 Intervention

Participants previously immunized against COVID-19 infection will be randomized to receive VXA-CoV2-3.1 (XBB.1.5 vaccine) tablet oral vaccine.

Group III: COMIRNATY® Safety Sentinel Cohort Active Control 1 Intervention

Participants previously immunized against COVID-19 infection will be randomized to receive COMIRNATY® (variant matched vaccine 2023-2024 formula) injectable COVID-19 vaccine.

Group IV: COMIRNATY® Active Control 1 Intervention

If no dose-related toxicities are observed, and upon the recommendation of the Data and Safety Monitoring Board following review of Day 31 safety data in the initial safety cohorts (and possibly immunogenicity data), enrollment will continue with the remaining participants who will be randomized to receive a single dose of 2024-2025 formula of COMIRNATY® mRNA COVID-19 injectable vaccine.

Who Is Running the Clinical Trial?

Vaxart

Lead Sponsor

Trials

22

Recruited

11,400+

Published Research Related to This Trial

The study found that administering live SARS-CoV-2 orally in rhesus macaques resulted in weak immunogenicity, with limited virus replication in the gastrointestinal tract and minimal mucosal antibody response.

Despite the weak immune response, there was some partial protection against respiratory SARS-CoV-2 challenges, indicating that while the oral vaccine shows potential, further optimization of the formulation and delivery method is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective Efficacy of Gastrointestinal SARS-CoV-2 Delivery against Intranasal and Intratracheal SARS-CoV-2 Challenge in Rhesus Macaques. Yu, J., Collins, ND., Mercado, NB., et al.[2022]

Moxifloxacin is a new fluoroquinolone antibiotic approved in the UK for treating adults with community-acquired pneumonia, acute exacerbation of chronic bronchitis, and acute sinusitis.

The drug is marketed as providing rapid relief from chest infections, highlighting its efficacy in managing respiratory tract infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moxifloxacin--a new fluoroquinolone antibacterial. [2018]

The study identified an effective oral COVID-19 vaccine candidate, rVSVΔG-Sdelta, which produced long-lasting neutralizing antibodies against multiple SARS-CoV-2 variants for up to one year.

In tests on golden hamsters, this vaccine demonstrated significant cross-protection against various strains of SARS-CoV-2, reducing viral replication and improving lung health after infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral delivery of a chitosan adjuvanted COVID-19 vaccine provides long-lasting and broad-spectrum protection against SARS-CoV-2 variants of concern in golden hamsters. Wang, S., Cui, H., Zhang, C., et al.[2023]

In a study of 1749 pneumonia patients treated with moxifloxacin, 89.4% showed significant clinical improvement by day 7, demonstrating its high efficacy as a treatment.

Moxifloxacin was well-tolerated, with 94.3% of patients rating its tolerability as 'very good' or 'good', and only 5.3% experiencing adverse events, indicating a strong safety profile for this antibiotic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of sequential intravenous/oral moxifloxacin therapy in pneumonia: results of the first post-marketing surveillance study with intravenous moxifloxacin in hospital practice. Barth, J., Stauch, K., Landen, H.[2018]

The MVA-CoV2-S vaccine candidate effectively protected K18-hACE2 transgenic mice from lethal SARS-CoV-2 infection, preventing virus replication in the lungs and reducing lung damage, indicating strong efficacy.

Two doses of the vaccine induced high levels of IgG and neutralizing antibodies against the virus and its variants, and also established long-term immune memory, suggesting potential for effective human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Full efficacy and long-term immunogenicity induced by the SARS-CoV-2 vaccine candidate MVA-CoV2-S in mice. Lázaro-Frías, A., Pérez, P., Zamora, C., et al.[2022]

In a study of 281 patients treated with intravenous antibiotics for bone and joint infections, 75% were found to be candidates for oral antibiotics, suggesting a potential shift in treatment practices.

Switching to oral antibiotics could save an average of $3,270.69 per patient, improving patient satisfaction and reducing the need for central vascular access, which is associated with complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Opportunities for Oral Antibiotic Therapy in Bone and Joint Infections. Bhagat, H., Sikka, MK., Sukerman, ES., et al.[2023]

The OVIVA study showed that oral antibiotics are just as effective as intravenous (IV) antibiotics for treating bone and joint infections, indicating a safe and effective alternative.

At our center, 79.7% of patients receiving outpatient parenteral antibiotic therapy (OPAT) for these infections could switch to oral antibiotics, resulting in a median savings of 19.5 days of IV treatment and approximately GBP 1234 per patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and Economic Impact of Implementing OVIVA Criteria on Patients With Bone and Joint Infections in Outpatient Parenteral Antimicrobial Therapy. Marks, M., Bell, LCK., Jones, I., et al.[2021]

The oral delivery of the rLVS ΔcapB/MN COVID-19 vaccine effectively protects hamsters from severe disease caused by high-dose SARS-CoV-2, showing comparable efficacy to other administration methods like intradermal and intranasal routes.

This vaccine targets conserved proteins of the virus, making it potentially effective against emerging variants, and its oral formulation could significantly improve vaccination rates, especially in low-resource settings where injectable vaccines are challenging to administer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Administration of Universal Bacterium-Vectored Nucleocapsid-Expressing COVID-19 Vaccine is Efficacious in Hamsters. Jia, Q., Bielefeldt-Ohmann, H., Maison, RM., et al.[2023]

Moxifloxacin administered through a nasogastric tube, whether with water or enteral feeding, showed no clinically significant changes in absorption, indicating that it can be safely given alongside enteral nutrition.

The study found that while there was a slight decrease in bioavailability when moxifloxacin was crushed and administered via a nasogastric tube, the differences were not statistically significant, suggesting that this method of administration is effective for patients in intensive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of enteral feeding on the oral bioavailability of moxifloxacin in healthy volunteers. Burkhardt, O., Stass, H., Thuss, U., et al.[2018]

The rVSV-based bivalent vaccine (v-EM2/SPΔC1Delta) administered orally elicited strong immune responses in mice, similar to those seen with intranasal immunization, including high levels of neutralizing antibodies against SARS-CoV-2 and effective responses against influenza A.

Oral immunization with this vaccine provided complete protection against the influenza H1N1 virus in mice, resulting in a 100% survival rate and significantly reduced lung viral loads, highlighting its potential as an effective mucosal vaccine for respiratory viruses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Immunization with rVSV Bivalent Vaccine Elicits Protective Immune Responses, Including ADCC, against Both SARS-CoV-2 and Influenza A Viruses. Ouyang, MJ., Ao, Z., Olukitibi, TA., et al.[2023]

Citations

1. acpjournals.org acpjournals.org/doi/10.7326/ANNALS-24-01015

Effectiveness of the 2023-to-2024 XBB.1.5 COVID-19 ... COVID-19 vaccines targeting the XBB.1.5 variant of Omicron were not effective in preventing infection and had relatively low VE against hospitalization and ...

2. thelancet.com thelancet.com/journals/laninf/article/PIIS1473-3099(24)00150-6/fulltext

Effectiveness of XBB.1.5 vaccines and antiviral drugs ... 1.5 vaccines and antiviral drugs reduced the risk of serious consequences of infection with SARS-CoV-2 omicron subvariants. XBB.1.5 vaccines ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06672055

NCT06672055 | A Study to Evaluate VXA-CoV2-3.3 COVID ... The primary objective of the study is to determine the relative efficacy of the investigational oral severe acute respiratory syndrome coronavirus 2 ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2835590

Estimated 2023-2024 COVID-19 Vaccine Effectiveness in ... In this study, the 2023-2024 COVID-19 vaccines were associated with fewer cases of medically attended COVID-19, with more robust outcomes for critical illness.

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2510226

Association of 2024–2025 Covid-19 Vaccine with ... Vaccine effectiveness against a composite of these outcomes was 28.3% (95% CI, 18.2 to 38.2), with a risk difference per 10,000 persons of 18.2 ...

6. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2815787

Adverse Events After XBB.1.5-Containing COVID-19 ... We investigated the association between the XBB.1.5-containing vaccine administered as a fifth COVID-19 vaccine dose and the risk of 28 adverse events.

7. fda.gov fda.gov/media/181494/download

Novavax COVID-19 Vaccine, Adjuvanted (2024-2025 ... In the Sponsor global safety database, cumulatively through July 31, 2024, the Sponsor received 5,682 individual case safety reports (ICSRs) ...

8. ausvaxsafety.org.au ausvaxsafety.org.au/covid-19-vaccines/pfizer-monovalent-omicron-xbb15-covid-19-vaccine-safety-data-all-participants

Pfizer monovalent Omicron XBB.1.5 COVID-19 vaccine ... Data on this page show the responses of individuals who received the Pfizer monovalent Omicron XBB.1.5 (age 12 years and over formulation) COVID-19 vaccine.

9. ir.novavax.com ir.novavax.com/press-releases/2024-04-01-Novavax-Presents-Data-on-Updated-COVID-19-Vaccine-and-Progress-to-Date-on-its-COVID-19-Influenza-Combination-Vaccine-Candidate-at-World-Vaccine-Congress-2024

Novavax Presents Data on Updated COVID-19 Vaccine ... Data also showed that the vaccine's safety and reactogenicity profile was consistent with its prototype vaccine (NVX-CoV2373). Differences ...