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

Study Overview
=================
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.

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

Conditions
-----------------
Covid19

Intervention / Treatment
-----------------
* Biological: VXA-CoV2-1


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female between the ages of 18 to 54 years, inclusive. Negative for SARS-CoV-2 infection at the time of screening In generally good health, without significant medical illness Demonstrates comprehension of the protocol procedures and is able to provide written informed consent. Available for all planned visits and willing to complete all protocol defined procedures and assessments Body mass index between 17 and 30 kg/m2 at screening. 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: 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). Is in a current occupation with high risk of exposure to SARS-CoV-2 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 Donation or use of blood or blood products within 4 weeks prior to vaccination or planned donation during the study period. Diagnosed bleeding disorder or significant bruising or bleeding difficulties that could make blood draws problematic. Any condition that resulted in the absence or removal of the spleen. Positive HIV, HBsAg or HCV tests at the screening visit. Stool sample with occult blood at screening. Use of antiviral medications, including anti-retrovirals, or any prescriptive medications for the prevention of COVID-19 within 7 days before vaccination 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 Regular use of nonsteroidal anti-inflammatory drugs, sulfonylureas, and angiotensin II blockers within 7 days before vaccination Acute disease within 72 hours prior to vaccination defined as the presence of a moderate or severe illness History of drug, alcohol or chemical abuse within 1 year of screening or positive urine drug screen for drugs of abuse at screening History of hypersensitivity or allergic reaction to any component of the investigational vaccine Administration of any investigational vaccine, drug or device within 8 weeks preceding vaccination 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: Laboratory values outside the range of normal for platelet counts and the following coagulation tests: PT/INR, aPTT, fibrinogen, and D-dimer. 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 54 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Open-label, repeat dose, dose ranging
Masking: None (Open Label)


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
VXA-C0V2-1, Vaxart oral vaccine, tablet vaccine, VXA-C0V2-1.1, Boost