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

• ClinicalTrials.gov Identifier: NCT04563702
• Recruitment Status: Completed
• First Posted: September 24, 2020
• Last Update Posted: January 20, 2023
• Sponsor: Vaxart
• Information provided by (Responsible Party): Vaxart

Tracking Information

• First Submitted Date: September 21, 2020
• First Posted Date: September 24, 2020
• Last Update Posted Date: January 20, 2023
• Actual Study Start Date: September 21, 2020
• Actual Primary Completion Date: October 10, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 23, 2020)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 23, 2020)

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

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: January 17, 2023)

• SARS-CoV-2 specific IgG/IgA by enzyme-linked immunosorbent assay [ Time Frame: Days 1, 29, 180 and 360 ]
  MSD
• Neutralizing antibody titers to SARS-CoV-2 [ Time Frame: Days 1, 29, 180 and 360 ]
  serum based assay of Ab titers
• Antigen-specific IgG/IgA antibody secreting assays (ASCs) [ Time Frame: Days 1 and Day 8 ]
  ELISpot
• Plasmablast immunophenotyping [ Time Frame: Day 1 and Day 8 ]
  Flow Cytometry
• Detection of antigen S-specific IgA [ Time Frame: Day 1 and Day 8 ]
  Flow Cytometry
• Detection of antigen S-specific IgA [ Time Frame: Days 1, 29, 180, and 360 ]
  Nasal swabs (SAM Device)
• Detection of antigen S-specific IgA [ Time Frame: Days 1, 29, 180, and 360 ]
  Saliva
• Cytof analysis of cell populations [ Time Frame: Day 1 and Day 8 ]
  Whole blood-based analysis
• IFN-g production/IL-4 production by T cells [ Time Frame: Day 1 and Day 8 ]
  fresh whole blood/TrueCulture tube

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: A Phase 1 Open-Label, Dose-Ranging Trial to Determine the Safety and Immunogenicity of an Adenoviral-Vector Based Vaccine (VXA-CoV2-1) Expressing a SARS-CoV-2 Antigen and dsRNA Adjuvant Administered Orally to Healthy Adult Volunteers VXA-CoV2-1.1-S Boost Substudy: Boost at 1 Year Post Initial Vaccination With an Adenoviral-Vector Based Vaccine VXA-CoV2-1.1-S Expressing a SARS-CoV-2 S Protein in a Subset of Subjects
• 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 Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Open-label, repeat dose, dose ranging

Masking: None (Open Label)
Primary Purpose: Prevention

• Condition: Covid19

Intervention

Biological: VXA-CoV2-1

non replicating Ad5 adjuvanted oral tableted vaccine

Study Arms

• Experimental: Low Dose 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
  Intervention: Biological: VXA-CoV2-1
• Experimental: High Dose
  High Dose (1E11 I.U.) of VXA-CoV2-1 oral tableted vaccine dispensed at Day 1
  Intervention: Biological: VXA-CoV2-1

• Publications *: Langel SN, Johnson S, Martinez CI, Tedjakusuma SN, Peinovich N, Dora EG, Kuehl PJ, Irshad H, Barrett EG, Werts AD, Tucker SN. Adenovirus type 5 SARS-CoV-2 vaccines delivered orally or intranasally reduced disease severity and transmission in a hamster model. Sci Transl Med. 2022 Aug 17;14(658):eabn6868. doi: 10.1126/scitranslmed.abn6868. Epub 2022 Aug 17.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 13, 2020): 35
• Original Estimated Enrollment (submitted: September 23, 2020): 48
• Actual Study Completion Date: October 10, 2021
• Actual Primary Completion Date: October 10, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 54 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04563702
• Other Study ID Numbers: VXA-COV2-101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided
• Plan Description: A plan on how to share individual subject's outcomes will be defined within the next few months.

• Current Responsible Party: Vaxart
• Original Responsible Party: Same as current
• Current Study Sponsor: Vaxart
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Vaxart
• Verification Date: September 2022