Covid19
Conditions
Keywords
VXA-C0V2-1, Vaxart oral vaccine, tablet vaccine, VXA-C0V2-1.1, Boost
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.
Interventions
BIOLOGICALVXA-CoV2-1
non replicating Ad5 adjuvanted oral tableted vaccine
Sponsors
Vaxart
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Open-label, repeat dose, dose ranging
Eligibility
Sex/Gender
ALL
Age
18 Years to 54 Years
Healthy volunteers
Yes
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)
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of solicited symptoms of reactogenicity | Day 1 through Day 8 post each immunization | Subject reported symptoms of local and systemic reactogenicity |
| Frequency of medically-attended adverse events (MAAEs) | Day 1 through Day 390 | Any adverse events reported following vaccination meeting definition of serious |
| Frequency of serious adverse events (SAEs) | Day 1 through Day 390 | Any adverse events reported following vaccination meeting definition of serious |
| Grade of unsolicited adverse events | Day 1 through Day 29 post each immunization | Any adverse events observed or reported following vaccination |
| Frequency of unsolicited adverse events | Day 1 through Day 29 post each immunization | Any adverse events observed or reported following vaccination |
| Grade of solicited symptoms of reactogenicity | Day 1 through Day 8 post each immunization | Subject reported symptoms of local and systemic reactogenicity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neutralizing antibody titers to SARS-CoV-2 | Day 1 through Day 390 | serum based assay of Ab titers |
| SARS-CoV-2 specific IgG/IgA | Day 1 through Day 390 | SARS-CoV-2 specific IgG/IgA by enzyme-linked immunosorbent assay (ELISA) |
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Neutralizing antibody titers to SARS-CoV-2 | Days 1, 29, 180 and 360 | serum based assay of Ab titers |
| IFN-g production/IL-4 production by T cells | Day 1 and Day 8 | fresh whole blood/TrueCulture tube |
| Cytof analysis of cell populations | Day 1 and Day 8 | Whole blood-based analysis |
| Detection of antigen S-specific IgA | Day 1 and Day 8 | Flow Cytometry |
| Plasmablast immunophenotyping | Day 1 and Day 8 | Flow Cytometry |
| SARS-CoV-2 specific IgG/IgA by enzyme-linked immunosorbent assay | Days 1, 29, 180 and 360 | MSD |
| Antigen-specific IgG/IgA antibody secreting assays (ASCs) | Days 1 and Day 8 | ELISpot |
Countries
United States
Outcome results
None listed