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Clinical Trials/NCT05067933
NCT05067933TerminatedPhase 2

A Phase 2, Double-Blind, Multi-Center, Randomized, Placebo-Controlled, Dose-Ranging Trial to Determine the Safety, Immunogenicity and Efficacy of an Adenoviral-Vector Based Vaccine Expressing Severe Acute Respiratory Syndrome (SARS-CoV-2) and dsRNA Adjuvant Administered Orally

Vaxart4 sites in 1 country66 target enrollmentStarted: October 22, 2021Last updated:
Conditions
Interventions
Drugs

Trial Snapshot

Phase
Phase 2
Status
Terminated
Sponsor
Vaxart
Enrollment
66
Locations
4
Primary Endpoint
Number of Participants Who Experienced a Solicited Symptom of Reactogenicity

Study Overview

Brief Summary

Part 1: An open label, dose and age escalation phase to evaluate the safety and immunogenicity of VXA-CoV2-1.1-S with a repeat-dose vaccination schedule in healthy adults aged 18 - 75 years old that are either vaccine naive or have received prior vaccination with an mRNA (messenger ribonucleic acid) vaccine for the prevention of COVID-19.

Part 2: This phase will assess the efficacy of prophylactic VXA-CoV2-1.1-S against confirmed COVID-19 occurring from 7 days after second dose with a repeat-dose vaccination schedule in healthy adults compared to placebo. Safety and immunogenicity of VXA-CoV2-1.1-S will also be evaluated in this phase.

Detailed Description

Part 1: This is an open-label, dose-ranging phase of the study to determine the safety and immunogenicity of an orally administered adenoviral-vector based vaccine (VXA-COV2-1.1-S) expressing a SARS-CoV-2 antigen and dsRNA adjuvant. Post screening activities, healthy adult volunteers, either naïve or prior vaccinated with an mRNA COVID-19 vaccine, aged 18 - 55 yrs old, and then 56 - 75 yrs old, will be enrolled into the study in 8 subgroups. Participants will receive either a low or a high dose of an oral tableted vaccine at Days 1 and Day 29. The 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. An independent data monitoring committee (IDMC) will provide safety oversight through the duration of the trial. Safety and immunogenicity data will inform on the dose selection for Part 2.

Part 2: This will be a placebo-controlled phase with the vaccine dose level selected from Part 1. Subjects will receive two doses of vaccine or placebo at Days 1 and 29. Subjects will be followed as in Part 1 for safety and immunogenicity. They will also be followed for 6 months for efficacy.

Study Design

Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential
Primary Purpose
Prevention
Masking
Triple (Participant, Care Provider, Investigator)

Masking Description

Double-Blind, Randomized (Part 2)

Eligibility Criteria

Ages
18 Years to 75 Years (Adult, Older Adult)
Sex
All
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  • Not provided

Exclusion Criteria

  • Not provided

Arms & Interventions

Part 1 Cohort 1a (Naïve, low dose, young adult)

Experimental

1E10 repeat-dose vaccinations with VXA-CoV2-1.1-S at Days 1 and 29 in young adults (18-55 yrs) who are vaccine naïve

Intervention: VXA-CoV2-1.1-S (Drug)

Part 1 Cohort 1b (Naïve, high dose, young adult)

Experimental

1E11 repeat-dose vaccinations with VXA-CoV2-1.1-S at Days 1 and 29 in young adults (18-55 yrs) who are vaccine naïve

Intervention: VXA-CoV2-1.1-S (Drug)

Part 1 Cohort 1c (Naïve, low dose, older adult)

Experimental

1E10 repeat-dose vaccinations with VXA-CoV2-1.1-S at Days 1 and 29 in older adults (56-75 yrs) who are vaccine naïve

Intervention: VXA-CoV2-1.1-S (Drug)

Part 1 Cohort 1d (Naïve, high dose, older adult)

Experimental

1E11 repeat-dose vaccinations with VXA-CoV2-1.1-S at Days 1 and 29 in older adults (56-75 yrs) who are vaccine naïve

Intervention: VXA-CoV2-1.1-S (Drug)

Part 1 Cohort 2a (Prior vaccinated, low dose, young adult)

Experimental

1E10 repeat-dose vaccinations with VXA-CoV2-1.1-S at Days 1 and 29 in young adults (18-55 yrs) who have received prior vaccinations with an mRNA vaccine

Intervention: VXA-CoV2-1.1-S (Drug)

Part 1 Cohort 2b (Prior vaccinated, high dose, young adult)

Experimental

1E11 repeat-dose vaccinations with VXA-CoV2-1.1-S at Days 1 and 29 in young adults (18-55 yrs) who have received prior vaccinations with an mRNA vaccine

Intervention: VXA-CoV2-1.1-S (Drug)

Part 1 Cohort 2c (Prior vaccinated, low dose, older adult)

Experimental

1E10 repeat-dose vaccinations with VXA-CoV2-1.1-S at Days 1 and 29 in older adults (56-75 yrs) who have received prior vaccinations with an mRNA vaccine

Intervention: VXA-CoV2-1.1-S (Drug)

Part 1 Cohort 2d (Prior vaccinated, high dose, older adult)

Experimental

1E11 repeat-dose vaccinations with VXA-CoV2-1.1-S at Days 1 and 29 in older adults (56-75 yrs) who have received prior vaccinations with an mRNA vaccine

Intervention: VXA-CoV2-1.1-S (Drug)

Part 2 Healthy Adults: Active vaccine

Experimental

Repeat dose vaccinations with VXA-CoV2-1.1-S at dose selected from Part 1 in healthy male and female adult volunteers 18 to 75 years old

Intervention: VXA-CoV2-1.1-S (Drug)

Part 2 Healthy Adults: Placebo control

Placebo Comparator

Repeat dose administration with matching placebo tablets in healthy male and female adult volunteers 18 to 75 years old

Intervention: Placebo Tablets (Other)

Outcomes

Primary Outcomes

Number of Participants Who Experienced a Solicited Symptom of Reactogenicity

Time Frame: Up to 7 days after Dose 1 (Days 1 to 8) and Dose 2 (Days 29 to 36)

Solicited symptoms of reactogenicity were predefined systemic signs and symptoms of reactogenicity for which the participant was specifically questioned, and which were noted by the participant in their daily Solicited Symptom Diary for 7 days after each vaccination, including: * fever (any temperature 100°F or higher) * headache * myalgia (muscle pain) * abdominal pain * anorexia (defined and not eating) * nausea * vomiting * diarrhea * malaise/fatigue

Severity of Solicited Symptoms of Reactogenicity

Time Frame: Up to 7 days after Dose 1 (Days 1 to 8) and Dose 2 (Days 29 to 36)

Solicited symptoms of reactogenicity were predefined systemic signs and symptoms of reactogenicity for which the participant was specifically questioned, and which were noted by the participant in their daily Solicited Symptom Diary for 7 days after each vaccination, including: * fever (any temperature 100°F or higher) * headache * myalgia (muscle pain) * abdominal pain * anorexia (defined and not eating) * nausea * vomiting * diarrhea * malaise/fatigue Participants were instructed to rate solicited symptoms of reactogenicity that were collected in their Solicited Symptom Diary with the below grades, against pre-defined criteria as noted in the protocol: * Grade 1 - Mild * Grade 2 - Moderate * Grade 3 - Severe * Grade 4 - Life Threatening Participants with multiple solicited symptoms were only counted once, the highest severity of which was used.

Number of Participants Who Experienced an Unsolicited Treatment-emergent Adverse Event (TEAE) During the Active Treatment Period

Time Frame: Day 1 to Day 57

A TEAE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention, occurring after first dose of study drug. A serious TEAE was any TEAE that met any of the following criteria: * Resulted in death. * Was life-threatening. * Required inpatient hospitalization or prolongation of existing hospitalization. * Resulted in persistent or significant disability/incapacity. * Was a congenital anomaly/birth defect. * Was a suspected transmission of any infectious agent via a medicinal product. * Was a significant medical event, as judged by the investigator.

Severity of Unsolicited TEAEs During the Active Treatment Period

Time Frame: Day 1 to Day 57

All unsolicited TEAEs during the active treatment period were assessed by the investigator using the below scale: * Mild: Events that required minimal or no treatment and did not interfere with the participant's daily activities. * Moderate: Events that resulted in a low level of inconvenience or concern with the therapeutic measures. Moderate events may have caused some interference with functioning. * Severe: Events that interrupted a participant's usual daily activity and may have required systemic drug therapy or other treatment. Severe events were usually incapacitating. * Life Threatening: Any adverse drug experience that placed the participant, in the view of the investigator, at immediate risk of death from the reaction as it occurred. Participants with multiple TEAEs during the active treatment period were only counted once, the highest severity of which was used.

Number of Participants Who Experienced a Medically Attended Adverse Event (MAAE) During the Active Treatment Period

Time Frame: Day 1 to Day 57

MAAEs were defined as TEAEs with medically-attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason. Routine study visits were not considered medically-attended visits. New onset of chronic illness/diseases (NOCI) and adverse events of special interest (AESIs) were collected as part of the MAAEs. As defined in the protocol, adverse events for potential immune-mediated medical conditions as well as events associated with thrombosis and thrombocytopenia were considered AESIs.

Severity of MAAEs During the Active Treatment Period

Time Frame: Day 1 to Day 57

All MAAEs during the active treatment period were assessed by the investigator using the below scale: * Mild: Events that required minimal or no treatment and did not interfere with the participant's daily activities. * Moderate: Events that resulted in a low level of inconvenience or concern with the therapeutic measures. Moderate events may have caused some interference with functioning. * Severe: Events that interrupted a participant's usual daily activity and may have required systemic drug therapy or other treatment. Severe events were usually incapacitating. * Life Threatening: Any adverse drug experience that placed the participant, in the view of the investigator, at immediate risk of death from the reaction as it occurred. Participants with multiple MAAEs during the active treatment period were only counted once, the highest severity of which was used.

Secondary Outcomes

  • Number of Participants Who Experienced a MAAE During the Safety Follow-up Period(From last dose up to 12 months post-last dose)
  • Severity of MAAEs During the Safety Follow-up Period(From last dose up to 12 months post-last dose)
  • Number of Participants Who Experienced a Serious TEAE During the Safety Follow-up Period(From last dose up to 12 months post-last dose)
  • Severity of Serious TEAEs During the Safety Follow-up Period(From last-dose up to 12 months post-last dose)
  • Levels of SARS-CoV2-specific Immunoglobulin G Spike (IgG-S) Antibodies by Mesoscale Discovery (MSD) Assay(Day 1, Day 29 and Day 57)
  • Levels of SARS-CoV2-specific Immunoglobulin G Nucleocapsid (IgG-N) Antibodies by MSD Assay(Day 1, Day 29 and Day 57)
  • Levels of SARS-CoV2-specific Immunoglobulin G Receptor-binding Domain (IgG-RBD) Antibodies by MSD Assay(Day 1, Day 29 and Day 57)
  • Levels of SARS-CoV2-specific Immunoglobulin A Spike (IgA-S) Antibodies by MSD Assay(Day 1, Day 29 and Day 57)
  • Levels of SARS-CoV2-specific Immunoglobulin A Nucleocapsid (IgA-N) Antibodies by MSD Assay(Day 1, Day 29 and Day 57)
  • Levels of SARS-CoV2-specific Immunoglobulin A Receptor-binding Domain (IgA-RBD) Antibodies by MSD Assay(Day 1, Day 29 and Day 57)
  • Levels of Neutralizing Serum Antibody Titers to SARS-CoV-2(Day 1, Day 29 and Day 57)
  • Mean Percentage of Cluster of Differentiation 8 (CD8) T-cells Making Tumor Necrosis Factor (TNF) Alpha+ Spike (S) as Measured by Intracellular Cytokine Cytometry (ICC)(Day 1, Day 8, Day 29 and Day 36)
  • Mean Percentage of CD8 T-cells Making Interferon (IFN) Gamma+S as Measured by ICC(Day 1, Day 8, Day 29 and Day 36)
  • Levels of SARS-CoV2-specific IgA-S Antibodies in Nasal Swabs(Day 1, Day 29 and Day 57)
  • Levels of SARS-CoV2-specific IgA-S Antibodies in Saliva Swabs(Day 1, Day 29 and Day 57)

Investigators

Sponsor
Vaxart
Sponsor Class
Industry
Responsible Party
Sponsor

Study Sites (4)

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