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This is a Phase 2b randomized, double-blind, placebo-controlled vaccination and challenge study to assess the protective efficacy of the Vaxart Norovirus vaccine (VXA-G1.1-NN). Healthy adults will be randomized in a 1:1 ratio to receive one oral dose of vaccine or placebo.
Approximately 28 days post-vaccination, subjects will be admitted to an isolation ward and challenged with the NV GI.1 Norwalk challenge strain. After challenge, subjects will be monitored for signs and symptoms of acute gastroenteritis (AGE) from Day 29 to discharge. At 4 days post challenge (Day 33) asymptomatic subjects will be discharged from the isolation ward and will be followed in a series of outpatient visits and telephone calls. Symptomatic subjects may be kept in the isolation ward for up to an additional 3 days.
Study Population Healthy male and female adult volunteers age 18 to 49 years inclusive with blood type O or A and who are confirmed H type-1 antigen secretory positive Investigational Product
Active Vaccine:
Placebo Control:
• Oral tablets similar in appearance and number to active vaccine tablets Multiple tablets of study drug will be dispensed to allow delivery of the intended vaccine dose (1x10E11 IU). A matching number of placebo tablets will be dispensed to maintain the study blinding.
Viral Challenge Inoculum
Study Hypothesis Norovirus vaccine (VXA-G1.1-NN) will protect against Norovirus Gastroenteritis (NVG) related to norovirus (NoV) infection in the challenge model
Approximately 120 subjects will be dosed in the vaccination phase to ensure at least 100 subjects (~ 50 VXA-G1.1-NN vaccine and 50 placebo) are available to participate in the challenge phase. Approximately 28 days post-vaccination, subjects will be admitted to an isolation ward and challenged with the NV GI.1 Norwalk challenge strain. After challenge, subjects will be monitored for signs and symptoms of acute gastroenteritis (AGE) from Day 29 to discharge. NV illness lasts 2-4 days and is self-limited. At 4 days post challenge (Day 33) asymptomatic subjects will be discharged from the isolation ward and will be followed in a series of outpatient visits and telephone calls. Symptomatic subjects may be kept in the isolation ward for up to an additional 3 days.
The following study visits and remote contacts will be conducted during the study
Vaccination Phase:
Challenge Phase:
Safety Follow-Up:
An independent Safety Monitoring Committee (SMC) will convene at pre-defined intervals during the norovirus challenge period, and also ad hoc as needed during the vaccination and challenge periods, to oversee the safety of the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active Vaccine Arm | Active Comparator | Subjects receiving Norovirus GI.1 Norwalk VP1 Vaccine, Oral E1-/E3-Deleted Replication Defective Recombinant Adenovirus 5 with dsRNA Adjuvant |
|
| Placebo Arm | Placebo Comparator | Subject receiving Placebo oral tablets similar in appearance and number to active vaccine tablets |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VXA-G1.1-NN | Biological | Norovirus GI.1 Norwalk VP1 Vaccine, Oral E1-/E3-Deleted Replication Defective Recombinant Adenovirus 5 with dsRNA Adjuvant |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Experienced Norovirus Gastroenteritis (NVG) | NVG is a composite endpoint defined as meeting both the definition of AGE and NV. AGE was defined as meeting any one of 3 criteria (diarrhea, vomiting, or diarrhea and vomiting) in any 24-hr rolling period. The individual criteria for diarrhea, vomiting, or diarrhea and vomiting were as follows: 1. Diarrhea: i. ≥ 3 loose or liquid stools in any 24-hr rolling period, or ii. 400 g of loose or liquid stools in any 24-hr rolling period 2. Vomiting: ≥ 2 vomiting episodes in any 24-hr rolling period, or 3. Diarrhea and vomiting: i. one vomiting episode plus any loose or liquid stool in any 24-hr rolling period ii. one vomiting episode plus ≥ 2 of the following events in any 24-hr rolling period:
| Up to approximately Day 57 |
| Levels of Viral Protein 1, Major Capsid, or Surface Protein of Viruses (VP1)-Specific Immunoglobulin A (IgA) Antibody-Secreting Cell (ASC) Against Norwalk at Day 8 | Blood samples were collected at different timepoints throughout the study. | Day 8 |
| Geometric Mean Titer (GMT) of Histo-blood Group Antigen (HBGA) Blocking Antibodies Against NV by Blocking Titer 50 (BT50) at Day 28 | Blood samples were collected at different timepoints throughout the study. A positive change indicates an increase in titers. | Day 28 |
| VP1-specific Serum Immunoglobulin G (IgG) Response at Day 28 | Blood samples were collected at different timepoints throughout the study. | Day 28 |
| VP1-specific Serum IgA at Day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Experienced Solicited Symptoms of Reactogenicity | Solicited symptoms of reactogenicity included:
| Up to Day 8 |
| Number of Participants Who Experienced Unsolicited Adverse Events (AEs) During the Vaccination Phase |
| Measure | Description | Time Frame |
|---|---|---|
| VP1 GI.1-specific Fecal IgA at Day 1, Day 28 and Day 57 | Fecal samples for immunogenicity assessments were collected on Day 1 (prior to vaccination), Day 28 (1 day prior to challenge), and Day 57 (28 days post-challenge). VP1 GI.1-specific IgA antibody values were normalized by the total IgA in each sample. | Day 1 (baseline), Day 28 and Day 57 |
Inclusion Criteria:
Male or female between the ages of 18 - 49 years, inclusive
Able to give written informed consent
Healthy, as determined by the principal investigator (PI) or PI in consultation with the research monitor and Sponsor Healthy = No clinically significant health concerns or medical illness, as determined by medical history, physical examination, vital signs, electrocardiogram (ECG), and clinical laboratories (complete blood count (CBC), chemistry and urinalysis)
Comprehension of the study requirements with ability and willingness to complete all assessments and comply with confinement period post viral challenge, and all scheduled visits and contacts
Confirmed blood type (A or O)
Demonstrated to be H type-1 antigen secretor positive (by saliva test)
Body mass index between 17 and 35 kg/m2, inclusive, at Screening
Female participants must have a negative pregnancy test at pre-vaccination and pre-challenge and fulfill one of the following Criteria:
i. A reliable form of contraception must be approved by the Investigator (eg, double barrier method, Depo-Provera, intrauterine device, Norplant, oral contraceptives, contraceptive patches) d. Not be sexually active (abstinent) or in a same sex relationship (must be discussed with site staff and documented)
Male subjects must agree not to father a child or donate sperm, as well as to use contraception/barrier (a male condom) or be abstinent from heterosexual intercourse, from vaccination through the active period (Day 57)
Exclusion Criteria:
Administration/use of any investigational drug or device 30 days prior to vaccination through the active period (Day 57)
Administration of any licensed vaccine within 30 days prior to vaccination or planned use of the above stated during the active period (through Day 57)
Presence of a significant medical condition, which, in the opinion of the investigator, precludes participation in the study. Significant medical condition = for example, psychiatric conditions, or gastrointestinal disease, such as peptic ulcer, symptoms or evidence of active gastritis or gastroesophageal reflux disease, inflammatory bowel disease, alcohol or illicit drug abuse/dependency, or other laboratory abnormalities
Laboratory values outside the range of normal for platelet counts and the following coagulation tests: prothromibin time test (PT/INR), activated partial thromboplastine time test (aPTT) and fibrinogen
Any of the following history or conditions that may lead to higher risk of clotting events and/or thrombocytopenia:
Family or personal history of bleeding or thrombosis
History of heparin-related thrombotic events, and/or receiving heparin treatments
History of autoimmune or inflammatory disease
Presence of any of the following conditions known to increase risk of thrombosis within 6 months prior to screening:
Any one of the following ECG findings within 45 days prior to vaccination:
Exclusionary ECG findings:
History of cancer or cancer treatment within past 3 years (excluding basal cell or squamous cell carcinomas)
Presence of immunosuppression or medical condition possibly associated with impaired immune responsiveness, including diabetes mellitus or angioedema
Donation or use of blood or blood products within 30 days prior to vaccination through the active period (Day 57)
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
Evidence of confirmed infection with human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) with confirmatory assays
Abnormal stool pattern (fewer than 3 bowel movements per week or more than 3 per day)
History of irritable bowel disease or inflammatory digestive or gastrointestinal condition that could affect the distribution / safety evaluation of an orally administered vaccine targeting the mucosa of the small intestine.
Such conditions may include but are not limited to:
Use of proton pump inhibitors, H2 blockers or antacids within 7 days prior to vaccination through the active period (Day 57)
Use of antibiotics within 30 days prior to vaccination through the active period (Day 57) Note: use of a brief (≤ 10 days) course of oral or topical antibiotic for minor upper respiratory infection (URI), urinary tract infection (UTI), dental work, or skin infection allowed within the screening period, but must be completed 7 days prior to first vaccination
Use of medication known to affect the immune function (e.g. systemic corticosteroids and others) within 14 days prior to vaccination through the active period (Day 57)
Regular use of nonsteroidal anti-inflammatory drugs within 7 days prior to vaccination through the active period (Day 57)
Use of over-the-counter probiotics or antidiarrheals within 7 days prior to vaccination through the active period (Day 57)
Evidence of recent (within 2 months of vaccination) or of current nonbacterial gastroenteritis suggestive of NV infection [vomiting or unformed or watery stools (> 2 during a 24-hour period)]
Any gastroenteritis within the past 2 weeks prior to vaccination
Acute disease within 72 hours prior to vaccination, defined as the presence of a moderate or severe illness with or without fever (as determined by the Investigator through medical history and physical examination). (Assessment may be repeated during screening period)
Presence of a fever ≥ 38ºC measured orally at baseline
History if hematochezia (blood in stool) or melena (black stool)
Any significant hospitalization within the last year which in the opinion of the investigator or sponsor could interfere with study participation
History of serious reactions to any vaccination such as anaphylaxis, respiratory problems, Guillain-Barre syndrome, hives or abdominal pain
History of a hypersensitivity or allergic reaction to any component of the investigational vaccine or placebo, including but not limited to fish gelatin. Subjects with known fish allergies should be excluded.
History of drug, alcohol or chemical abuse within 1 year prior to vaccination
Positive test for drugs of abuse or alcohol at screening, vaccination baseline and pre-challenge (except for previous marijuana use; concurrent or ongoing use of marijuana during the active study period).
Consistent/habitual smoking within 2 months prior to vaccination (defined as smoking ≥ 1 pack of cigarettes a day). Smoking is not permitted during the inpatient stay
Other conditions, in the clinical judgment of the investigator, that would jeopardize the safety or rights of a subject or interfere with the evaluation of the study
Social/Occupational:
Living with or having daily contact with children < 5 years old or women known to be pregnant or nursing; this includes significant contact at home, school, day-care, or equivalent facilities
Living with or having daily contact with elderly persons > 70 years of age or infirmed, diapered individuals, persons with disabilities or incontinence; this includes at work or visits to nursing homes and day-care or equivalent facilities
Employment in the food service industry such as restaurant or cafeteria facilities; specifically, this includes persons whose employment requires food handling and processing in the 4 weeks following viral challenge
Health-care workers with patient contact expected in the 4 weeks following viral challenge
Expected contact, via employment or at home, with immunocompromised persons in the 4 weeks following viral challenge. Immunocompromised persons = HIV-positive, receiving immunosuppressive medications such as oral steroids, anti-neoplastic agents
Presence of household members who have received the Ad4 or Ad7 vaccines within 2 months prior to vaccination
Employment as an airline flight attendant or cruise ship crew, scheduled to work in the 4 weeks following challenge
Persons planning to live in a confined environment (eg, a cruise, camp, etc.) in the 4 weeks following viral challenge
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| Name | Affiliation | Role |
|---|---|---|
| James Cummings, MD | Vaxart, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| AltaSciences LA | Cypress | California | 90630 | United States |
Healthy participants were randomized in a 1:1 ratio to receive a single oral dose of VXA-G1.1-NN or placebo. The total study duration for each participant was approximately 16 months, including screening, a 28-day vaccination phase, a 28-day Challenge Phase, and up to 365 days of safety follow-up.
Participants were enrolled at 1 center in the United States (US) between December 2021 and October 2023.
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| ID | Title | Description |
|---|---|---|
| FG000 | VXA-G1.1-NN | Healthy participants received a single dose of VXA-G1.1-NN oral vaccine tablet. Approximately 29 days post-vaccination, participants began the Challenge Phase Day 1. During this phase, participants were isolated, exposed to the Norwalk virus (NV) genogroup I genotype 1 (GI.1) Norwalk challenge strain, and monitored for signs and symptoms of acute gastroenteritis (AGE) until discharge. Asymptomatic participants were discharged on Day 3 of the Challenge Phase and continued with a series of outpatient visits and telephone follow-ups. Symptomatic participants could remain in isolation for up to an additional 3 days. |
| FG001 | Placebo | Healthy participants received a single dose of matching placebo. Approximately 29 days post-vaccination, participants began the Challenge Phase Day 1. During this phase, participants were isolated, exposed to the NV GI.1 Norwalk challenge strain, and monitored for signs and symptoms of AGE until discharge. Asymptomatic participants were discharged on Day 3 of the Challenge Phase and continued with a series of outpatient visits and telephone follow-ups. Symptomatic participants could remain in isolation for up to an additional 3 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Full Analysis Population (FAP): all randomized participants analyzed by randomized vaccination group assignment, who received study vaccination (active or placebo), and had available data for the specified analysis.
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| ID | Title | Description |
|---|---|---|
| BG000 | VXA-G1.1-NN | Healthy participants received a single dose of VXA-G1.1-NN oral vaccine tablet. Approximately 29 days post-vaccination, participants began the Challenge Phase Day 1. During this phase, participants were isolated, exposed to the NV GI.1 Norwalk challenge strain, and monitored for signs and symptoms of AGE until discharge. Asymptomatic participants were discharged on Day 3 of the Challenge Phase and continued with a series of outpatient visits and telephone follow-ups. Symptomatic participants could remain in isolation for up to an additional 3 days. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Who Experienced Norovirus Gastroenteritis (NVG) | NVG is a composite endpoint defined as meeting both the definition of AGE and NV. AGE was defined as meeting any one of 3 criteria (diarrhea, vomiting, or diarrhea and vomiting) in any 24-hr rolling period. The individual criteria for diarrhea, vomiting, or diarrhea and vomiting were as follows: 1. Diarrhea: i. ≥ 3 loose or liquid stools in any 24-hr rolling period, or ii. 400 g of loose or liquid stools in any 24-hr rolling period 2. Vomiting: ≥ 2 vomiting episodes in any 24-hr rolling period, or 3. Diarrhea and vomiting: i. one vomiting episode plus any loose or liquid stool in any 24-hr rolling period ii. one vomiting episode plus ≥ 2 of the following events in any 24-hr rolling period:
| FAP: all randomized participants analyzed by randomized vaccination group assignment, who received study vaccination (active or placebo), and had available data for the specified analysis. | Posted | Count of Participants | Participants | Up to approximately Day 57 |
Up to approximately 16 months
Safety Population: consisted of all participants who received any study vaccination (active or placebo). This population was summarized according to the actual vaccination received.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | VXA-G1.1-NN | Healthy participants received a single dose of VXA-G1.1-NN oral vaccine tablet. Approximately 29 days post-vaccination, participants began the Challenge Phase Day 1. During this phase, participants were isolated, exposed to the NV GI.1 Norwalk challenge strain, and monitored for signs and symptoms of AGE until discharge. Asymptomatic participants were discharged on Day 3 of the Challenge Phase and continued with a series of outpatient visits and telephone follow-ups. Symptomatic participants could remain in isolation for up to an additional 3 days. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Deep vein thrombosis | Vascular disorders | MedDRA (Unspecified) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Maria Apkarian | Vaxart | +1 (650) 779-4560 | mapkarian@vaxart.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 25, 2023 | Feb 4, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D017250 | Caliciviridae Infections |
| ID | Term |
|---|---|
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
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| Placebo Tablets | Other | Oral tablets similar in appearance and number to active vaccine tablets |
|
| Norovirus GI.1 Norwalk Virus Inoculum | Biological | Norwalk Virus Inoculum Lot 01-09NV |
|
Blood samples were collected at different timepoints throughout the study.
| Day 28 |
Unsolicited AEs referred to any AEs that occurred during a clinical trial but were not specifically pre-defined or actively sought by the study protocol. Unsolicited AEs could include any medical condition or symptom, whether or not it was related to the intervention being studied. |
| Up to Day 28 of Vaccination Phase (28-days phase) |
| Number of Participants Who Experienced Serious AEs (SAEs), AEs of Specific Interest (AESIs), and New Onsets of Chronic Illness (NOCIs) | A SAE was any AE that resulted in one or more of the following outcomes: death, a life-threatening event where the subject was at immediate risk of death (not hypothetically), inpatient hospitalization or the prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of normal life functions, congenital abnormality or birth defect, or an important medical event that, that jeopardized the participant's health or required medical or surgical intervention to prevent a serious outcome. A NOCI was defined as the diagnosis post-study drug administration of a new medical condition, which was chronic in nature, including those potentially controllable by medication (e.g., diabetes, asthma). | Up to approximately 12 months post vaccination |
| Number of Participants Who Experienced Unsolicited AEs During the Challenge Phase | Unsolicited AEs referred to any AEs that occurred during a clinical trial but were not specifically pre-defined or actively sought by the study protocol. Unsolicited AEs could include any medical condition or symptom, whether or not it was related to the intervention being studied. | Up to Day 29 of Challenge Phase (28-days phase) |
| Number of Participants With AGE During the Inpatient Challenge Phase | AGE was defined as meeting any one of 3 criteria (diarrhea, vomiting, or diarrhea and vomiting) in any 24-hr rolling period. The individual criteria for diarrhea, vomiting, or diarrhea and vomiting were as follows: 1. Diarrhea: i. ≥ 3 loose or liquid stools produced in any 24-hr rolling period, or ii. 400 g of loose or liquid stools produced in any 24-hr rolling period 2. Vomiting: ≥ 2 vomiting episodes in any 24-hr rolling period, or 3. Diarrhea and vomiting: i. one vomiting episode plus any loose or liquid stool in any 24-hr rolling period ii. one vomiting episode plus ≥ 2 of the following events in any 24-hr rolling period:
| Day 28 of Challenge Phase (28-days phase) |
| Severity of AGE Assessed Using the Modified Vesikari Scale | The Modified Vesikari Scale is a tool used to assess the severity of AGE by evaluating symptoms such as diarrhea, vomiting, fever, and dehydration. It scores these symptoms based on their frequency and severity, with a minimum score of 0 and a maximum score of 20, where higher scores indicate more severe symptoms and lower scores suggest milder or no symptoms and severity. | Up to approximately Day 36 |
| Number of Participants Who Experienced Moderate or Severe Gastroenteritis | Moderate or severe gastroenteritis was defined by cumulative loose stools ≥ 1000gr during the inpatient period. | Up to approximately Day 57 |
| Duration of AGE | Time to onset of AGE was calculated as the time from challenge administration to the first recorded instance of an event satisfying the criteria for AGE. AGE was defined as meeting any of the 3 criteria: 1. Diarrhea: i. ≥ 3 loose or liquid stools in any 24-hr rolling period, or ii. 400 g of loose or liquid stools in any 24-hr rolling period 2. Vomiting: ≥ 2 vomiting episodes in any 24-hr rolling period, or 3. Diarrhea and vomiting: i. one vomiting episode plus any loose or liquid stool in any 24-hr rolling period ii. one vomiting episode plus ≥ 2 of the following events in any 24-hr rolling period:
| Up to approximately Day 57 |
| Number of Participants Who Experienced Incidences of Diarrhea or Emesis | Classification of diarrhea was done through grading stools with Grade 3 (thick liquid stool) to Grade 5 (clear water diarrheal stool) being considered diarrhea. | Up to approximately Day 57 |
| Number of Participants With Norovirus (NoV) Infection up to Challenge Period Day 8 | NoV infection was defined as a positive qRT-PCR in stool or emesis up to Challenge Period Day 8, and the presence of NV antigen in stool. | Challenge Phase Day 8 (equal to Study Day 36) |
| Geometric Mean Genome Copies (GCs) of NoV Shedding in Stool Measured by qRT-PCR | NoV shedding was assessed by qRT-PCR. Stool samples were reported on 10^3 copies/gm. If a participant produced multiple results for a given study day, the result with the largest shedding response was used for analysis. Samples that were reported as "Not Quantifiable" or as lower than the limit of detection (LOD) were analyzed as ½2*LOD (76.2). | Pre-challenge up to Day 8 of Challenge Phase (equal to Study Day 36) |
| Geometric Mean GCs of NoV Shedding in Emesis Measured by qRT-PCR | NoV shedding was assessed by qRT-PCR. Emesis samples were reported in 10^3 copies/mL. If a participant produced multiple results for a given study day, the result with the largest shedding response was used for analysis. Samples that were reported as "Not Quantifiable" or as lower than the limit of detection (LOD) were analyzed as ½2*LOD (15.3). | Pre-challenge up to Day 8 of Challenge Phase (equal to Study Day 36) |
| Duration of NoV Infection | Duration of NoV Infection was defined as the time from NoV infection to the time of resolution of infection, defined as a negative qRT-PCR result not followed by a positive qRT-PCR result. | Up to approximately Day 57 |
| VP1 GI.1-specific Saliva IgA at Day 1, Day 28 and Day 57 |
Saliva samples were collected on Day 1 (prior to vaccination), Day 28 (1 day prior to challenge), and Day 57 (28 days post-challenge). VP1 GI.1-specific IgA antibody values were normalized by the total IgA in each sample. |
| Day 1 (baseline), Day 28 and Day 57 |
| Other |
|
| BG001 | Placebo | Healthy participants received a single dose of matching placebo. Approximately 29 days post-vaccination, participants began the Challenge Phase Day 1. During this phase, participants were isolated, exposed to the NV GI.1 Norwalk challenge strain, and monitored for signs and symptoms of AGE until discharge. Asymptomatic participants were discharged on Day 3 of the Challenge Phase and continued with a series of outpatient visits and telephone follow-ups. Symptomatic participants could remain in isolation for up to an additional 3 days. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | VXA-G1.1-NN | Healthy participants received a single dose of VXA-G1.1-NN oral vaccine tablet. Approximately 29 days post-vaccination, participants began the Challenge Phase Day 1. During this phase, participants were isolated, exposed to the NV GI.1 Norwalk challenge strain, and monitored for signs and symptoms of AGE until discharge. Asymptomatic participants were discharged on Day 3 of the Challenge Phase and continued with a series of outpatient visits and telephone follow-ups. Symptomatic participants could remain in isolation for up to an additional 3 days. |
| OG001 | Placebo | Healthy participants received a single dose of matching placebo. Approximately 29 days post-vaccination, participants began the Challenge Phase Day 1. During this phase, participants were isolated, exposed to the NV GI.1 Norwalk challenge strain, and monitored for signs and symptoms of AGE until discharge. Asymptomatic participants were discharged on Day 3 of the Challenge Phase and continued with a series of outpatient visits and telephone follow-ups. Symptomatic participants could remain in isolation for up to an additional 3 days. |
|
|
| Primary | Levels of Viral Protein 1, Major Capsid, or Surface Protein of Viruses (VP1)-Specific Immunoglobulin A (IgA) Antibody-Secreting Cell (ASC) Against Norwalk at Day 8 | Blood samples were collected at different timepoints throughout the study. | Immunogenicity Population: all randomized participants who received study vaccination (active or placebo), and had available data for the specified analysis. | Posted | Mean | 95% Confidence Interval | cells/10^6 PBMCs | Day 8 |
|
|
|
| Primary | Geometric Mean Titer (GMT) of Histo-blood Group Antigen (HBGA) Blocking Antibodies Against NV by Blocking Titer 50 (BT50) at Day 28 | Blood samples were collected at different timepoints throughout the study. A positive change indicates an increase in titers. | Immunogenicity Population: all randomized participants who received study vaccination (active or placebo), and had available data for the specified analysis. | Posted | Geometric Mean | 95% Confidence Interval | Geometric mean titer | Day 28 |
|
|
|
| Primary | VP1-specific Serum Immunoglobulin G (IgG) Response at Day 28 | Blood samples were collected at different timepoints throughout the study. | Immunogenicity Population: all randomized participants who received study vaccination (active or placebo), and had available data for the specified analysis. | Posted | Geometric Mean | 95% Confidence Interval | AU/mL | Day 28 |
|
|
|
| Primary | VP1-specific Serum IgA at Day 28 | Blood samples were collected at different timepoints throughout the study. | Immunogenicity Population: all randomized participants who received study vaccination (active or placebo), and had available data for the specified analysis. | Posted | Geometric Mean | 95% Confidence Interval | AU/mL | Day 28 |
|
|
|
| Secondary | Number of Participants Who Experienced Solicited Symptoms of Reactogenicity | Solicited symptoms of reactogenicity included:
| Safety Population: consisted of all participants who received any study vaccination (active or placebo). This population was summarized according to the actual vaccination received. | Posted | Count of Participants | Participants | Up to Day 8 |
|
|
|
| Secondary | Number of Participants Who Experienced Unsolicited Adverse Events (AEs) During the Vaccination Phase | Unsolicited AEs referred to any AEs that occurred during a clinical trial but were not specifically pre-defined or actively sought by the study protocol. Unsolicited AEs could include any medical condition or symptom, whether or not it was related to the intervention being studied. | Vaccination Phase Safety Population: consisted of all participants who received any study vaccination (active or placebo). This population was summarized according to the actual vaccination received. | Posted | Count of Participants | Participants | Up to Day 28 of Vaccination Phase (28-days phase) |
|
|
|
| Secondary | Number of Participants Who Experienced Serious AEs (SAEs), AEs of Specific Interest (AESIs), and New Onsets of Chronic Illness (NOCIs) | A SAE was any AE that resulted in one or more of the following outcomes: death, a life-threatening event where the subject was at immediate risk of death (not hypothetically), inpatient hospitalization or the prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of normal life functions, congenital abnormality or birth defect, or an important medical event that, that jeopardized the participant's health or required medical or surgical intervention to prevent a serious outcome. A NOCI was defined as the diagnosis post-study drug administration of a new medical condition, which was chronic in nature, including those potentially controllable by medication (e.g., diabetes, asthma). | Safety Population: consisted of all participants who received any study vaccination (active or placebo). This population was summarized according to the actual vaccination received. | Posted | Count of Participants | Participants | Up to approximately 12 months post vaccination |
|
|
|
| Secondary | Number of Participants Who Experienced Unsolicited AEs During the Challenge Phase | Unsolicited AEs referred to any AEs that occurred during a clinical trial but were not specifically pre-defined or actively sought by the study protocol. Unsolicited AEs could include any medical condition or symptom, whether or not it was related to the intervention being studied. | Challenge Phase Safety Population: consisted of all participants who received any study vaccination (active or placebo) and entered the 28-days Challenge Phase. This population was summarized according to the actual vaccination received. | Posted | Count of Participants | Participants | Up to Day 29 of Challenge Phase (28-days phase) |
|
|
|
| Secondary | Number of Participants With AGE During the Inpatient Challenge Phase | AGE was defined as meeting any one of 3 criteria (diarrhea, vomiting, or diarrhea and vomiting) in any 24-hr rolling period. The individual criteria for diarrhea, vomiting, or diarrhea and vomiting were as follows: 1. Diarrhea: i. ≥ 3 loose or liquid stools produced in any 24-hr rolling period, or ii. 400 g of loose or liquid stools produced in any 24-hr rolling period 2. Vomiting: ≥ 2 vomiting episodes in any 24-hr rolling period, or 3. Diarrhea and vomiting: i. one vomiting episode plus any loose or liquid stool in any 24-hr rolling period ii. one vomiting episode plus ≥ 2 of the following events in any 24-hr rolling period:
| Challenge Phase FAP: consisted of all participants who received any study vaccination (active or placebo) and entered the 28-days Challenge Phase. This population was summarized according to the actual vaccination received. | Posted | Count of Participants | Participants | Day 28 of Challenge Phase (28-days phase) |
|
|
|
| Secondary | Severity of AGE Assessed Using the Modified Vesikari Scale | The Modified Vesikari Scale is a tool used to assess the severity of AGE by evaluating symptoms such as diarrhea, vomiting, fever, and dehydration. It scores these symptoms based on their frequency and severity, with a minimum score of 0 and a maximum score of 20, where higher scores indicate more severe symptoms and lower scores suggest milder or no symptoms and severity. | Challenge Phase FAP: consisted of all participants who received any study vaccination (active or placebo) and entered the 28-days Challenge Phase. This population was summarized according to the actual vaccination received. | Posted | Mean | 95% Confidence Interval | Score on scale | Up to approximately Day 36 |
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| Secondary | Number of Participants Who Experienced Moderate or Severe Gastroenteritis | Moderate or severe gastroenteritis was defined by cumulative loose stools ≥ 1000gr during the inpatient period. | Challenge Phase FAP: consisted of all participants who received any study vaccination (active or placebo) and entered the 28-days Challenge Phase. This population was summarized according to the actual vaccination received. | Posted | Count of Participants | Participants | Up to approximately Day 57 |
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| Secondary | Duration of AGE | Time to onset of AGE was calculated as the time from challenge administration to the first recorded instance of an event satisfying the criteria for AGE. AGE was defined as meeting any of the 3 criteria: 1. Diarrhea: i. ≥ 3 loose or liquid stools in any 24-hr rolling period, or ii. 400 g of loose or liquid stools in any 24-hr rolling period 2. Vomiting: ≥ 2 vomiting episodes in any 24-hr rolling period, or 3. Diarrhea and vomiting: i. one vomiting episode plus any loose or liquid stool in any 24-hr rolling period ii. one vomiting episode plus ≥ 2 of the following events in any 24-hr rolling period:
| Challenge Phase FAP: consisted of all participants who received any study vaccination (active or placebo) and entered the 28-days Challenge Phase. This population was summarized according to the actual vaccination received. Only AGE positive participants were included in the analysis | Posted | Median | Full Range | Hours | Up to approximately Day 57 |
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| Secondary | Number of Participants Who Experienced Incidences of Diarrhea or Emesis | Classification of diarrhea was done through grading stools with Grade 3 (thick liquid stool) to Grade 5 (clear water diarrheal stool) being considered diarrhea. | Challenge Phase FAP: consisted of all participants who received any study vaccination (active or placebo) and entered the 28-days Challenge Phase. This population was summarized according to the actual vaccination received. | Posted | Count of Participants | Participants | Up to approximately Day 57 |
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| Secondary | Number of Participants With Norovirus (NoV) Infection up to Challenge Period Day 8 | NoV infection was defined as a positive qRT-PCR in stool or emesis up to Challenge Period Day 8, and the presence of NV antigen in stool. | Challenge Phase FAP: consisted of all participants who received any study vaccination (active or placebo) and entered the 28-days Challenge Phase. This population was summarized according to the actual vaccination received. | Posted | Count of Participants | Participants | Challenge Phase Day 8 (equal to Study Day 36) |
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| Secondary | Geometric Mean Genome Copies (GCs) of NoV Shedding in Stool Measured by qRT-PCR | NoV shedding was assessed by qRT-PCR. Stool samples were reported on 10^3 copies/gm. If a participant produced multiple results for a given study day, the result with the largest shedding response was used for analysis. Samples that were reported as "Not Quantifiable" or as lower than the limit of detection (LOD) were analyzed as ½2*LOD (76.2). | Challenge Phase FAP: consisted of all participants who received any study vaccination (active or placebo) and entered the 28-days Challenge Phase. This population was summarized according to the actual vaccination received. Only participants with available data at each time point were included. | Posted | Geometric Mean | 95% Confidence Interval | 10^3 copies/gm | Pre-challenge up to Day 8 of Challenge Phase (equal to Study Day 36) |
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| Secondary | Geometric Mean GCs of NoV Shedding in Emesis Measured by qRT-PCR | NoV shedding was assessed by qRT-PCR. Emesis samples were reported in 10^3 copies/mL. If a participant produced multiple results for a given study day, the result with the largest shedding response was used for analysis. Samples that were reported as "Not Quantifiable" or as lower than the limit of detection (LOD) were analyzed as ½2*LOD (15.3). | Challenge Phase FAP: consisted of all participants who received any study vaccination (active or placebo) and entered the 28-days Challenge Phase. This population was summarized according to the actual vaccination received. Only participants with available data at each time point were included. | Posted | Geometric Mean | 95% Confidence Interval | 10^3 copies/mL | Pre-challenge up to Day 8 of Challenge Phase (equal to Study Day 36) |
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| Secondary | Duration of NoV Infection | Duration of NoV Infection was defined as the time from NoV infection to the time of resolution of infection, defined as a negative qRT-PCR result not followed by a positive qRT-PCR result. | Challenge Phase FAP: consisted of all participants who received any study vaccination (active or placebo) and entered the 28-days Challenge Phase. This population was summarized according to the actual vaccination received. Only AGE positive participants were included in the analysis | Posted | Median | 95% Confidence Interval | Hours | Up to approximately Day 57 |
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| Other Pre-specified | VP1 GI.1-specific Fecal IgA at Day 1, Day 28 and Day 57 | Fecal samples for immunogenicity assessments were collected on Day 1 (prior to vaccination), Day 28 (1 day prior to challenge), and Day 57 (28 days post-challenge). VP1 GI.1-specific IgA antibody values were normalized by the total IgA in each sample. | Immunogenicity Population: all randomized participants who received study vaccination (active or placebo), and had available data for the specified analysis. | Posted | Geometric Mean | 95% Confidence Interval | μg/mg | Day 1 (baseline), Day 28 and Day 57 |
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| Other Pre-specified | VP1 GI.1-specific Saliva IgA at Day 1, Day 28 and Day 57 | Saliva samples were collected on Day 1 (prior to vaccination), Day 28 (1 day prior to challenge), and Day 57 (28 days post-challenge). VP1 GI.1-specific IgA antibody values were normalized by the total IgA in each sample. | Immunogenicity Population: all randomized participants who received study vaccination (active or placebo), and had available data for the specified analysis. | Posted | Geometric Mean | 95% Confidence Interval | μg/mg | Day 1 (baseline), Day 28 and Day 57 |
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| 0 |
| 86 |
| 0 |
| 86 |
| 55 |
| 86 |
| EG001 | Placebo | Healthy participants received a single dose of matching placebo. Approximately 29 days post-vaccination, participants began the Challenge Phase Day 1. During this phase, participants were isolated, exposed to the NV GI.1 Norwalk challenge strain, and monitored for signs and symptoms of AGE until discharge. Asymptomatic participants were discharged on Day 3 of the Challenge Phase and continued with a series of outpatient visits and telephone follow-ups. Symptomatic participants could remain in isolation for up to an additional 3 days. | 0 | 79 | 1 | 79 | 47 | 79 |
| Cellulitis | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Malaise | General disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
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Not provided
| All NOCI |
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