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

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

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.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Biological: 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
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • WCCT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 54 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Biological: VXA-CoV2-1; non replicating Ad5 adjuvanted oral tableted vaccine
Experimental: High Dose; High Dose (1E11 I.U.) of VXA-CoV2-1 oral tableted vaccine dispensed at Day 1	Biological: VXA-CoV2-1; non replicating Ad5 adjuvanted oral tableted vaccine

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Vaxart

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2020
• Primary Completion (Actual): October 10, 2021
• Study Completion (Actual): October 10, 2021

Study Registration Dates

• First Submitted: September 21, 2020
• First Submitted That Met QC Criteria: September 23, 2020
• First Posted (Actual): September 24, 2020

Study Record Updates

• Last Update Posted (Actual): January 20, 2023
• Last Update Submitted That Met QC Criteria: January 17, 2023
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: VXA-C0V2-1; Vaxart oral vaccine; tablet vaccine; Boost; VXA-C0V2-1.1
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: VXA-COV2-101

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No