Oral Vaccine for COVID-19

Recruiting at 144 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

10400 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the oral COVID-19 vaccine treatment VXA-CoV2-3.1?

Research on similar oral vaccines shows they can trigger strong immune responses and protect against COVID-19 in animal studies, suggesting potential effectiveness for VXA-CoV2-3.1. ^{1 2 3 4 5}

What makes the oral COVID-19 vaccine VXA-CoV2-3.1 unique compared to other COVID-19 treatments?

The oral COVID-19 vaccine VXA-CoV2-3.1 is unique because it is administered by mouth, unlike most COVID-19 vaccines which are given as injections. This could make it easier to distribute and administer, especially in areas with limited healthcare resources. ^{6 7 8 9 10}

What is the purpose of this trial?

The primary objective of the study is to determine the relative efficacy of the investigational oral severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccine tablet VXA-CoV2-3.3 compared to a currently recommended vaccine for the prevention of symptomatic Coronavirus Disease 2019 (COVID-19). In order to represent a more recently circulating SARS-CoV-2 variant, the main study endpoints will now evaluate the VXA-CoV2-3.3 (KP.2 strain) vaccine, and not the VXA-CoV2-3.1 (XBB.1.5 strain) vaccine.

Research Team

James Cummings, MD

Principal Investigator

Vaxart, Inc.

Eligibility Criteria

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.

I tested negative for COVID-19 before starting the trial.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

References

1. Netherlands 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. [2023]

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

Protective Efficacy of Gastrointestinal SARS-CoV-2 Delivery against Intranasal and Intratracheal SARS-CoV-2 Challenge in Rhesus Macaques. [2022]

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

Oral Administration of Universal Bacterium-Vectored Nucleocapsid-Expressing COVID-19 Vaccine is Efficacious in Hamsters. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Full efficacy and long-term immunogenicity induced by the SARS-CoV-2 vaccine candidate MVA-CoV2-S in mice. [2022]

5. Switzerland 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. [2023]

6. New Zealand 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. [2018]

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

Evaluation of Opportunities for Oral Antibiotic Therapy in Bone and Joint Infections. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of enteral feeding on the oral bioavailability of moxifloxacin in healthy volunteers. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Moxifloxacin--a new fluoroquinolone antibacterial. [2018]

10. United States 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. [2021]