A Ph 2 Trial With an Oral Tableted COVID-19 Vaccine
- Conditions
- COVID-19
- Interventions
- Drug: VXA-CoV2-1.1-SOther: Placebo Tablets
- Registration Number
- NCT05067933
- Lead Sponsor
- Vaxart
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 66
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1 Cohort 2a (Prior vaccinated, low dose, young adult) VXA-CoV2-1.1-S 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 Part 1 Cohort 1a (Naïve, low dose, young adult) VXA-CoV2-1.1-S 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 Part 1 Cohort 1b (Naïve, high dose, young adult) VXA-CoV2-1.1-S 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 Part 1 Cohort 2c (Prior vaccinated, low dose, older adult) VXA-CoV2-1.1-S 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 Part 1 Cohort 1c (Naïve, low dose, older adult) VXA-CoV2-1.1-S 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 Part 1 Cohort 2d (Prior vaccinated, high dose, older adult) VXA-CoV2-1.1-S 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 Part 2 Healthy Adults: Placebo control Placebo Tablets Repeat dose administration with matching placebo tablets in healthy male and female adult volunteers 18 to 75 years old Part 1 Cohort 1d (Naïve, high dose, older adult) VXA-CoV2-1.1-S 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 Part 1 Cohort 2b (Prior vaccinated, high dose, young adult) VXA-CoV2-1.1-S 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 Part 2 Healthy Adults: Active vaccine VXA-CoV2-1.1-S 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
- Primary Outcome Measures
Name Time Method Number of Participants Who Experienced a Solicited Symptom of Reactogenicity 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/fatigueSeverity of Solicited Symptoms of Reactogenicity 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 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 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 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 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 Outcome Measures
Name Time Method Number of Participants Who Experienced a MAAE During the Safety Follow-up Period From last dose up to 12 months post-last dose 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. NOCI and 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 Safety Follow-up Period From last dose up to 12 months post-last dose All MAAEs during the safety follow-up 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 safety follow-up period were only counted once, the highest severity of which was used.Number of Participants Who Experienced a Serious TEAE During the Safety Follow-up Period From last dose up to 12 months post-last dose 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 Serious TEAEs During the Safety Follow-up Period From last-dose up to 12 months post-last dose All serious 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 serious TEAEs during the active treatment period were only counted once, the highest severity of which was used.Levels of SARS-CoV2-specific Immunoglobulin G Spike (IgG-S) Antibodies by Mesoscale Discovery (MSD) Assay Day 1, Day 29 and Day 57 SARS-CoV2-specific IgG-S antibody levels were measured on specific timepoints via MSD assay. For results below the lower limit of quantification (LLOQ), the value was replaced with 1/2 the numeric portion of the original result rounded up to nearest integer. For results above the upper limit of quantification (ULOQ), the value was replaced with the numeric portion of the original result.
Levels of SARS-CoV2-specific Immunoglobulin G Nucleocapsid (IgG-N) Antibodies by MSD Assay Day 1, Day 29 and Day 57 SARS-CoV2-specific IgG-N antibody levels were measured on specific timepoints via MSD assay. For results below the LLOQ, the value was replaced with 1/2 the numeric portion of the original result rounded up to nearest integer. For results above the ULOQ, the value was replaced with the numeric portion of the original result.
Levels of SARS-CoV2-specific Immunoglobulin G Receptor-binding Domain (IgG-RBD) Antibodies by MSD Assay Day 1, Day 29 and Day 57 SARS-CoV2-specific IgG-RBD antibody levels were measured on specific timepoints via MSD assay. For results below the LLOQ, the value was replaced with 1/2 the numeric portion of the original result rounded up to nearest integer. For results above the ULOQ, the value was replaced with the numeric portion of the original result.
Levels of SARS-CoV2-specific Immunoglobulin A Spike (IgA-S) Antibodies by MSD Assay Day 1, Day 29 and Day 57 SARS-CoV2-specific IgA-S antibody levels were measured on specific timepoints via MSD assay. For results below the LLOQ, the value was replaced with 1/2 the numeric portion of the original result rounded up to nearest integer. For results above the ULOQ, the value was replaced with the numeric portion of the original result.
Levels of SARS-CoV2-specific Immunoglobulin A Nucleocapsid (IgA-N) Antibodies by MSD Assay Day 1, Day 29 and Day 57 SARS-CoV2-specific IgA-N antibody levels were measured on specific timepoints via MSD assay. For results below the LLOQ, the value was replaced with 1/2 the numeric portion of the original result rounded up to nearest integer. For results above the ULOQ, the value was replaced with the numeric portion of the original result.
Levels of SARS-CoV2-specific Immunoglobulin A Receptor-binding Domain (IgA-RBD) Antibodies by MSD Assay Day 1, Day 29 and Day 57 SARS-CoV2-specific IgA-RBD antibody levels were measured on specific timepoints via MSD assay. For results below the LLOQ, the value was replaced with 1/2 the numeric portion of the original result rounded up to nearest integer. For results above the ULOQ, the value was replaced with the numeric portion of the original result.
Levels of Neutralizing Serum Antibody Titers to SARS-CoV-2 Day 1, Day 29 and Day 57 Neutralizing Serum Antibody Titers to SARS-CoV-2 were measured on specific timepoints via qualified pseudovirus assay. For results below the LLOQ, the value was replaced with 1/2 the numeric portion of the original result rounded up to nearest integer. For results above the ULOQ, the value was replaced with the numeric portion of the original result.
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 TNF alpha+S were measured on specific timepoints via ICC. For results below the LLOQ, the value was replaced with 1/2 the numeric portion of the original result rounded up to nearest integer. For results above the ULOQ, the value was replaced with the numeric portion of the original result.
Mean Percentage of CD8 T-cells Making Interferon (IFN) Gamma+S as Measured by ICC Day 1, Day 8, Day 29 and Day 36 Mean Percentage of CD8 T-cells making IFN gamma+S were measured on specific timepoints via ICC. For results below the LLOQ, the value was replaced with 1/2 the numeric portion of the original result rounded up to nearest integer. For results above the ULOQ, the value was replaced with the numeric portion of the original result.
Levels of SARS-CoV2-specific IgA-S Antibodies in Nasal Swabs Day 1, Day 29 and Day 57 SARS-CoV2-specific IgA-S antibody levels in nasal swabs were measured on specific timepoints via MSD assay. For results below the LLOQ, the value was replaced with 1/2 the numeric portion of the original result rounded up to nearest integer. For results above the ULOQ, the value was replaced with the numeric portion of the original result.
Levels of SARS-CoV2-specific IgA-S Antibodies in Saliva Swabs Day 1, Day 29 and Day 57 SARS-CoV2-specific IgA-S antibody levels in saliva swabs were measured on specific timepoints via MSD assay. For results below the LLOQ, the value was replaced with 1/2 the numeric portion of the original result rounded up to nearest integer. For results above the ULOQ, the value was replaced with the numeric portion of the original result.
Trial Locations
- Locations (4)
Velocity Clinical Research, Inc,
🇺🇸Cleveland, Ohio, United States
AMR Knoxville
🇺🇸Knoxville, Tennessee, United States
AMR Wichita East
🇺🇸Wichita, Kansas, United States
Ark Clinical Research
🇺🇸Long Beach, California, United States