Safety and Immunogenicity Trial of an Oral SARS-CoV-2 Vaccine (VXA-CoV2-1) for Prevention of COVID-19 in Healthy Adults and Boost (VXA-CoV2-1.1-S) at 1 Year Post Initial Vaccination in Subset of Subjects

Phase 1

Completed

• Conditions: Covid19
• Interventions: Biological: VXA-CoV2-1

• Registration Number: NCT04563702
• Lead Sponsor: Vaxart

Brief Summary

VXA-CoV2-1 is a non-replicating Ad5 vector adjuvanted oral tableted vaccine being developed to prevent COVID-19, the disease resulting from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) infection. The study is designed to evaluate the safety and immunogenicity of VXA-CoV2-1 vaccine with repeat dosing at multiple dose levels. Safety and immunogenicity will be evaluated for up to 12 months after the second dose of VXA-CoV2-1.

Detailed Description

This is an open-label, dose-ranging trial to determine the safety and immunogenicity of an orally administered adenoviral-vector based vaccine (VXA-COV2-1) expressing a SARS-CoV-2 antigen and dsRNA adjuvant. Post screening activities, healthy adult volunteers aged 18 - 54 yrs old, inclusive, will be enrolled into the study. Participants will receive an oral dose of vaccine at Days 1 and a subject will also receive a second dose at Day 29; total study period will last \~ 2 months during the active phase, with a total 12 month safety follow-up period post last vaccination. Safety, reactogenicity and immunogenicity assessments will be performed at set times during the study active and follow-up periods. Subjects will be monitored for symptoms of COVID-19 throughout the duration of the study follow-up period.

Approximately 10 healthy male and female adult volunteers 18 to 54 years old who were enrolled in the main study will be included in a boost extension substudy for an additional 12 months from dosing for a total participation period of 24-25 months.

Study Timeline

• Study Start: 2020-09-21
• Study First Submitted: 2020-09-21
• Study First Submitted QC: 2020-09-23
• Study First Posted: 2020-09-24
• Primary Completion: 2021-10-10
• Study Completion: 2021-10-10
• Status Verified: 2022-09
• Last Update Submitted: 2024-06-20
• Last Update Posted: 2024-06-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

1. Male or female between the ages of 18 to 54 years, inclusive.
2. Negative for SARS-CoV-2 infection at the time of screening
3. In generally good health, without significant medical illness
4. Demonstrates comprehension of the protocol procedures and is able to provide written informed consent.
5. Available for all planned visits and willing to complete all protocol defined procedures and assessments
6. Body mass index between 17 and 30 kg/m2 at screening.
7. Female subjects must have a negative pregnancy test at screening and before each vaccination and fulfill an acceptable method of birth control (per protocol)

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Exclusion Criteria

1. Known previous exposure to SARS-CoV-2 or receipt of an investigational product for the prevention or treatment of COVID-19, middle east respiratory syndrome (MERS), or severe acute respiratory syndrome (SARS).

2. Is in a current occupation with high risk of exposure to SARS-CoV-2

3. Individuals with the following underlying medical conditions who are at higher risk (or might be at higher risk) of severe illness from COVID-19 per the CDC's guidance

4. Donation or use of blood or blood products within 4 weeks prior to vaccination or planned donation during the study period.

5. Diagnosed bleeding disorder or significant bruising or bleeding difficulties that could make blood draws problematic.

6. Any condition that resulted in the absence or removal of the spleen.

7. Positive HIV, HBsAg or HCV tests at the screening visit.

8. Stool sample with occult blood at screening.

9. Use of antiviral medications, including anti-retrovirals, or any prescriptive medications for the prevention of COVID-19 within 7 days before vaccination

10. Use of antibiotics, proton pump inhibitors, H2 blockers or antacids or medications known to affect the immune function within 7 to 14 days before vaccination

11. Regular use of nonsteroidal anti-inflammatory drugs, sulfonylureas, and angiotensin II blockers within 7 days before vaccination

12. Acute disease within 72 hours prior to vaccination defined as the presence of a moderate or severe illness

13. History of drug, alcohol or chemical abuse within 1 year of screening or positive urine drug screen for drugs of abuse at screening

14. History of hypersensitivity or allergic reaction to any component of the investigational vaccine

15. Administration of any investigational vaccine, drug or device within 8 weeks preceding vaccination

16. Any other condition that in the clinical judgment of the investigator would jeopardize the safety or rights of a subject participating in the trial, would render the subject unable to comply with the protocol or would interfere with the evaluation of the study endpoints.

    For subjects being re-evaluated for participation in the VXA-CoV2-1.1-S boost substudy the following will also be exclusionary:

17. Laboratory values outside the range of normal for platelet counts and the following coagulation tests: PT/INR, aPTT, fibrinogen, and D-dimer.

18. Any of the following history or conditions that may lead to higher risk of clotting events and/or thrombocytopenia:

    e. Family or personal history of bleeding or thrombosis f. History of heparin-related thrombotic events, and/or receiving heparin treatments g. History of autoimmune or inflammatory disease h. Presence of any of the following conditions known to increase risk of thrombosis within 6 months prior to screening:

    • Recent surgery other than removal/biopsy of cutaneous lesions
    • Immobility (confined to bed or wheelchair for 3 or more successive days)
    • Head trauma with loss of consciousness or documented brain injury
    • Receipt of anticoagulants for prophylaxis of thrombosis
    • Recent clinically significant infection

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Low Dose VXA-CoV2-1	VXA-CoV2-1	Low dose (1E10 I.U.) of VXA-CoV2-1 oral tableted vaccine dispensed at Day 1. A subset will also receive a second dose at Day 29
High Dose	VXA-CoV2-1	High Dose (1E11 I.U.) of VXA-CoV2-1 oral tableted vaccine dispensed at Day 1

Primary Outcome Measures

Name	Time	Method
Frequency of solicited symptoms of reactogenicity	Day 1 through Day 8 post each immunization	Subject reported symptoms of local and systemic reactogenicity
Frequency of serious adverse events (SAEs)	Day 1 through Day 390	Any adverse events reported following vaccination meeting definition of serious
Grade of solicited symptoms of reactogenicity	Day 1 through Day 8 post each immunization	Subject reported symptoms of local and systemic reactogenicity
Frequency of unsolicited adverse events	Day 1 through Day 29 post each immunization	Any adverse events observed or reported following vaccination
Grade of unsolicited adverse events	Day 1 through Day 29 post each immunization	Any adverse events observed or reported following vaccination
Frequency of medically-attended adverse events (MAAEs)	Day 1 through Day 390	Any adverse events reported following vaccination meeting definition of serious

Secondary Outcome Measures

Name	Time	Method
SARS-CoV-2 specific IgG/IgA	Day 1 through Day 390	SARS-CoV-2 specific IgG/IgA by enzyme-linked immunosorbent assay (ELISA)
Neutralizing antibody titers to SARS-CoV-2	Day 1 through Day 390	serum based assay of Ab titers
Antigen-specific IgG/IgA antibody secreting (ASCs)	Day 1 through Day 44	ASCs by ELISpot
Th1/Th2 polarization	Day 1 through Day 44	Flow Cytometry

Trial Locations

Locations (1)

WCCT; 🇺🇸 Cypress, California, United States