Norovirus InfectionsPhase 1VXA-NVV-104NCT04854746
Ph 1b: Safety & Immunogenicity of Ad5 Based Oral Norovirus Vaccine
A Phase 1 study testing VXA-GI.1.NN in people with Norovirus Infections, run by Vaxart at 3 sites in United States.
Trial summary
A Phase 1b, multicenter, randomized, double-blind, placebo-controlled study to determine the safety and immunogenicity of an adenoviral-vector based oral norovirus vaccine expressing GI.1 VP1 administered orally to healthy older adult volunteers 55-80 years of age. Read more about this study
- Who is it for?
- Ages 55 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Norovirus Infections
- What is being tested?
- VXA-GI.1.NN
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 3 sitesUnited States
- Study dates
- 26 Apr 2021to 4 Jan 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- To be eligible for this study, participants must meet all the following:
- Age
- 55 to 80 years old inclusive at the time of signing the Informed Consent Form (ICF).
- Type of Participants
- In stable and good general health, without significant medical illness, based on medical history, physical examination and vital signs at screening
- Safety laboratory values within the following range criteria at screening:
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- Laboratory value of < grade 1 elevation from normal or decrease from normal with no clinical significance (NCS) for alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin,
- Laboratory value of < grade 1 from normal with no NCS for:
- decreased: albumin, magnesium, total protein and phosphorous
- elevated: amylase, BUN, CPK and creatine and;
- elevated or decreased: calcium, glucose, potassium and sodium;
- Body mass index (BMI) between 17 and 35 kg/m2 at screening
- Available for all planned visits and phone calls, and willing to complete all protocol- defined procedures and assessments (including ability and willingness to swallow multiple small enteric-coated tablets per study dose).
- Gender and Reproductive Considerations
- Male or female participants Female participants must provide a negative pregnancy test at screening and baseline or be at least one year post-menopausal or surgically sterile. Female participants of childbearing potential must be willing to use a reliable oral, implantable, transdermal or injectable contraceptive for 30 days prior to and until 60 days post last study drug administration. The form of contraception must be approved by the Investigator Contraception use by men should be consistent with local regulations regarding the methods of contraception for participants in clinical studies.
- Informed Consent
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Who cannot join
- The participants must be excluded from participating in the study if they meet any of the following:
- Medical Conditions
- Presence of significant uncontrolled medical or psychiatric illness (acute or chronic) including institution of new medical/surgical treatment or significant dose alteration for uncontrolled symptoms or drug toxicity within 3 months of screening and reconfirmed at baseline
- Cancer, or treatment for cancer treatment, within past 3 years (excluding basal cell carcinoma or squamous cell carcinoma)
- Presence of immunosuppression or medical condition possibly associated with impaired immune responsiveness, including diabetes mellitus
- History of irritable bowel disease or other inflammatory digestive or gastrointestinal condition that could affect the distribution/safety evaluation of an orally administered vaccine targeting the mucosa of the small intestine.
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- Such conditions may include but are not limited to:
- Esophageal Motility Disorder
- Malignancy
- Malabsorption
- Pancreaticobiliary disorders
- Irritable bowel syndrome
- Inflammatory Bowel Disease
- Surgical Resection
- GERD
- Hiatal Hernia
- Peptic Ulcer (History of cholecystectomy is not exclusionary)
- History of any form of angioedema
- History of serious reactions to vaccination such as anaphylaxis, respiratory problems, hives or abdominal pain
- 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
- Acute disease within 72 hours prior to vaccination defined as the presence of a moderate or severe illness (as determined by the Investigator through medical history and physical exam). (Assessment may be repeated during screening period.)
- Presence of a fever ≥ 38oC measured orally at baseline (Assessment may be repeated during screening period)
- Any significant hospitalization within the last year which in the opinion of the investigator or sponsor could interfere with study participation.
- 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:
- 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
- Any other condition that in the clinical judgment of the investigator would jeopardize the safety or rights of a participant taking in the study, would render the participant unable to comply with the protocol or would interfere with the evaluation of the study endpoints Diagnostic Assessments
- Positive human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) tests at the screening visit
- Stool sample with occult blood at screening
- Positive urine drug screen for drugs of abuse at screening (postive test for marijuana is not exclusionary; however concurrent use of marijuana during the study Active period through Day 57 is prohibited)
- Positive breath or urine alcohol test at screening and baseline Prior/Concurrent Therapy
- Receipt of a licensed vaccine (including any COVID-19 vaccines under Emergency Use Authorization) within 14 days prior to baseline vaccination or planned administration during the study active period (Day 57)
- Use of antibiotics, proton pump inhibitors, H2 blockers or antacids within 7 days prior to study drug administration or planned use during the active study period (Day 57)
- Use of medications known to affect the immune function (e.g., systemic corticosteroids and others) within 2 weeks before study drug administration or planned use during the active study period (Day 57)
- Daily use of nonsteroidal anti-inflammatory drugs within 7 days prior to study drug administration or planned use during the active study period (Day 57)
- Administration of any investigational vaccine, drug or device within 8 weeks preceding study drug administration, or planned use within the duration of the study Other Exclusions
- Donation or use of blood or blood products within 30 days prior to study drug administration or planned donation during the active study period (Day 57)
- History of drug, alcohol or chemical abuse within 1 year of screening
- History of hypersensitivity or allergic reaction to any component of the investigational vaccine, including but not limited to fish gelatin
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Benchmark Research
Austin, Texas, 78705
WCCT
Cypress, California, 90630
Benchmark Research
New Orleans, Louisiana, 70006
About this study
Official title: A Phase 1b, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Determine the Safety and Immunogenicity of an Adenoviral-vector Based Oral Norovirus Vaccine Expressing GI.1 VP1 Administered Orally to Health Stable Older Adult Volunteers 55-80 Years of Age
A Phase 1b, multicenter, randomized, double-blind, placebo-controlled study to determine the safety and immunogenicity of an adenoviral-vector based oral norovirus vaccine expressing GI.1 VP1 administered orally to healthy older adult volunteers 55-80 years of age. The study is designed to assess the safety, tolerability, immunogenicity, and efficacy of 3 dose levels of vaccine with a 2-dose vaccination schedule (4 weeks apart) in healthy older adults (55 to 80 years old)
Read the detailed description
A Phase 1b, multicenter, randomized, double-blind, placebo-controlled study to determine the safety and immunogenicity of an adenoviral-vector based oral norovirus vaccine expressing GI.1 VP1 administered orally to healthy older adult volunteers 55-80 years of age. The study is designed to assess the safety, tolerability, immunogenicity, and efficacy of 3 dose levels of vaccine with a 2-dose vaccination schedule (4 weeks apart) in healthy older adults (55 to 80 years old).
Subjects will we randomized in the study utilizing an age and dose escalation schedule. A Safety Monitoring Committee will provide oversight of the trial throughout the duration of the study.
- Conditions
- Norovirus Infections
- Being tested
- VXA-GI.1.NN, Placebo Tablet
- Keywords
- norovirus, oral vaccine, elderly
- Medical subject headings
- Caliciviridae Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VXA-GI.1.NNBiological
GI.1 oral vaccine tablet
Placebo TabletBiological
Tablets matching in number and appearance to active vaccine tablets
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 Low Dose Active | Active comparator | VXA-GI.1-NN tableted vaccine group, 2 doses (Day 1 and Day 29) at 1x10Log10 Receives: Biological: VXA-GI.1.NN |
| Cohort 3 High Dose Active | Active comparator | VXA-GI.1 tableted vaccine group, 2 doses (Day 1 and Day 29) at 1x10Log11 Receives: Biological: VXA-GI.1.NN |
| Cohort 1 Low Dose Placebo | Placebo comparator | Placebo tablets matching in number and appearance to active vaccine doses. Receives: Biological: Placebo Tablet |
| Cohort 3 High Dose Placebo | Placebo comparator | Placebo tablets matching in number and appearance to active vaccine doses. Receives: Biological: Placebo Tablet |
| Cohort 2 Medium Dose Active | Active comparator | VXA-GI.1 tableted vaccine group, 2 doses (Day 1 and Day 29) at 3x10Log10 Receives: Biological: VXA-GI.1.NN |
| Cohort 2 Medium Dose Placebo | Placebo comparator | Placebo tablets matching in number and appearance to active vaccine doses. Receives: Biological: Placebo Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Solicited Adverse Events
Safety
Measured: Day 1 (Vaccination) to 7 days post vaccination
Rate of Unsolicited Adverse Events
Safety
Measured: Day 1 (Vaccination) to 28 days post vaccination
Secondary outcomes (3)
VP1 specific IgA ASC
Immunogenicity
Measured: Day 1 (Vaccination) to 7 days post vaccination
Norovirus GI.1 histo-blood group antigen GBGA blocking antibodies (BT50)
Immunogenicity
Measured: Day 1 (Vaccination) to 7 days post vaccination
VP1 specific serum IgG
Immunogenicity
Measured: Day 1 (Vaccination) to 7 days post vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2021
- Study start26 Apr 2021
- Primary completion4 Jan 2022
- Study completion4 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Norovirus InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vaxart
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David Liebowitz, MD, PhD, Study chair, Vaxart, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04854746
- Sponsor's protocol ID
- VXA-NVV-104
- Acronym
- VXA-NVV-104
- Status last verified
- Feb 2023
- First submitted
- 19 Apr 2021
- Last updated
- 13 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Study results will be summarized and presented by treatment arm comparisons. Individual subject data will not be shared with other researchers.
Publications
Flitter BA, Greco SN, Lester CA, Neuhaus ED, Tedjakusuma SN, Shriver M, Cuevas-Juarez E, Gutierrez S, Braun MR, Pasetti MF, Tucker SN, Cummings JF. An oral norovirus vaccine tablet was safe and elicited mucosal immunity in older adults in a phase 1b clinical trial. Sci Transl Med. 2025 Mar 5;17(788):eads0556. doi: 10.1126/scitranslmed.ads0556. Epub 2025 Mar 5.
PubMed 40043138
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Determine the Safety and Immunogenicity of an Adenoviral-vector Based Oral Norovirus Vaccine Expressing GI.1 VP1 Administered Orally to Health Stable Older Adult Volunteers 55-80 Years of Age
- ClinicalTrials.gov ID
- NCT04854746
- Acronym / sponsor ID
- VXA-NVV-104 / VXA-NVV-104
- Conditions
- Norovirus Infections
- Keywords
- norovirus, oral vaccine, elderly
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- VaxartIndustry (pharma, biotech, devices)
- Study start
- 26 Apr 2021 (actual)
- Primary completion
- 4 Jan 2022 (actual)
- Study completion
- 4 Jan 2022 (actual)
- First posted
- 22 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase 1b, multicenter, randomized, double-blind, placebo-controlled study to determine the safety and immunogenicity of an adenoviral-vector based oral norovirus vaccine expressing GI.1 VP1 administered orally to healthy older adult volunteers 55-80 years of age. The study is designed to assess the safety, tolerability, immunogenicity, and efficacy of 3 dose levels of vaccine with a 2-dose vaccination schedule (4 weeks apart) in healthy older adults (55 to 80 years old)
Detailed description
A Phase 1b, multicenter, randomized, double-blind, placebo-controlled study to determine the safety and immunogenicity of an adenoviral-vector based oral norovirus vaccine expressing GI.1 VP1 administered orally to healthy older adult volunteers 55-80 years of age. The study is designed to assess the safety, tolerability, immunogenicity, and efficacy of 3 dose levels of vaccine with a 2-dose vaccination schedule (4 weeks apart) in healthy older adults (55 to 80 years old).
Subjects will we randomized in the study utilizing an age and dose escalation schedule. A Safety Monitoring Committee will provide oversight of the trial throughout the duration of the study.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 Low Dose Active | Active comparator | Biological: VXA-GI.1.NNVXA-GI.1-NN tableted vaccine group, 2 doses (Day 1 and Day 29) at 1x10Log10 |
| Cohort 3 High Dose Active | Active comparator | Biological: VXA-GI.1.NNVXA-GI.1 tableted vaccine group, 2 doses (Day 1 and Day 29) at 1x10Log11 |
| Cohort 1 Low Dose Placebo | Placebo comparator | Biological: Placebo TabletPlacebo tablets matching in number and appearance to active vaccine doses. |
| Cohort 3 High Dose Placebo | Placebo comparator | Biological: Placebo TabletPlacebo tablets matching in number and appearance to active vaccine doses. |
| Cohort 2 Medium Dose Active | Active comparator | Biological: VXA-GI.1.NNVXA-GI.1 tableted vaccine group, 2 doses (Day 1 and Day 29) at 3x10Log10 |
| Cohort 2 Medium Dose Placebo | Placebo comparator | Biological: Placebo TabletPlacebo tablets matching in number and appearance to active vaccine doses. |
Who may qualify
- Ages
- 55 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Age
- 55 to 80 years old inclusive at the time of signing the Informed Consent Form (ICF).
- Type of Participants
- In stable and good general health, without significant medical illness, based on medical history, physical examination and vital signs at screening
- Safety laboratory values within the following range criteria at screening:
Key exclusion criteria (47 listed)
- The participants must be excluded from participating in the study if they meet any of the following:
- Medical Conditions
- Presence of significant uncontrolled medical or psychiatric illness (acute or chronic) including institution of new medical/surgical treatment or significant dose alteration for uncontrolled symptoms or drug toxicity within 3 months of screening and reconfirmed at baseline
- Cancer, or treatment for cancer treatment, within past 3 years (excluding basal cell carcinoma or squamous cell carcinoma)
- Presence of immunosuppression or medical condition possibly associated with impaired immune responsiveness, including diabetes mellitus
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VXA-GI.1.NNGI.1 oral vaccine tablet | Biological | Cohort 1 Low Dose Active, Cohort 2 Medium Dose Active, Cohort 3 High Dose Active |
| Placebo TabletTablets matching in number and appearance to active vaccine tablets | Biological | Cohort 1 Low Dose Placebo, Cohort 2 Medium Dose Placebo, Cohort 3 High Dose Placebo |
Primary outcome
Rate of Solicited Adverse Events
Time frame: Day 1 (Vaccination) to 7 days post vaccination
Safety
Rate of Unsolicited Adverse Events
Time frame: Day 1 (Vaccination) to 28 days post vaccination
Safety
3 secondary outcomes
VP1 specific IgA ASC
Time frame: Day 1 (Vaccination) to 7 days post vaccination
Norovirus GI.1 histo-blood group antigen GBGA blocking antibodies (BT50)
Time frame: Day 1 (Vaccination) to 7 days post vaccination
VP1 specific serum IgG
Time frame: Day 1 (Vaccination) to 7 days post vaccination
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2023.
- Derived from this study: PubMed 40043138Flitter BA, Greco SN, Lester CA, Neuhaus ED, Tedjakusuma SN, Shriver M, Cuevas-Juarez E, Gutierrez S, Braun MR, Pasetti MF, Tucker SN, Cummings JF. An oral norovirus vaccine tablet was safe and elicited mucosal immunity in older adults in a phase 1b clinical trial. Sci Transl Med. 2025 Mar 5;17(788):eads0556. doi: 10.1126/scitranslmed.ads0556. Epub 2025 Mar 5.
- Individual participant dataSharing planned: No. Study results will be summarized and presented by treatment arm comparisons. Individual subject data will not be shared with other researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Liebowitz, MD, PhD study chair
Vaxart, Inc.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VXA-GI.1.NN in people with Norovirus Infections, run by Vaxart at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 47 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Solicited Adverse Events (time frame: Day 1 (Vaccination) to 7 days post vaccination). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04854746, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2023.