A Study to Evaluate Vaxart's Oral Bivalent GI.1/GII.4 Norovirus Vaccine in Healthy Lactating Females and Their Nursing Infants

NCT07254728 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: VXA-NVV-108
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 5

Brief Summary

The primary objective of this study is to evaluate the safety and tolerability of an oral bivalent GI.1/GII.4 norovirus vaccine administration in healthy lactating female participants and to assess the short-term immunogenicity of oral bivalent GI.1/GII.4 norovirus vaccine administration in healthy lactating female participants and its association with the immunogenicity response in breastmilk.

Conditions

Norovirus Infections

Keywords

Healthy participants; VXA-G1.1-NN; VXA-G2.4-NS

Outcome Measures

Primary Outcomes (18)

• Number of Participants (Mothers) With Any Solicited Symptoms of Reactogenicity for 1 Week Following Trial Dose

  Solicited symptoms of reactogenicity were predefined adverse events (AEs) for which the participant was specifically questioned, and which were noted by the participant in their solicited symptom diary, including: fever (any temperature 100°F or higher), headache, myalgia (muscle pain), abdominal pain, anorexia (defined as not eating), nausea, vomiting, diarrhea, and malaise/fatigue. The severity of each solicited symptom of reactogenicity was graded by the participant as mild, moderate, severe or life-threatening.

  1 week post study dose (8 days)

• Number of Participants (Mothers) With Unsolicited Treatment-emergent Adverse Events (TEAEs)

  TEAEs:AEs that began after start of an investigational product or an already present event that worsens in intensity or frequency following intervention.An AE considered serious (SAE) if,in view of Investigator or Sponsor,it resulted in death,life-threatening AE,inpatient hospitalization/prolongation of hospitalization,persistent or significant incapacity or disability disrupting normal life functions,congenital anomaly/birth defect,or an important medical event which based upon medical judgment may have jeopardized participant and required intervention to prevent 1 of outcomes.AESIs:serious/non-serious AEs of scientific and medical concern with potential immune mediated conditions and events associated with thrombosis and thrombocytopenia.NOCI:diagnosis post-enrollment and vaccination of new chronic medical condition,including those controllable by medication.An AE was unsolicited if it did not fulfill conditions prelisted in eCRF in terms of diagnosis/onset window post-vaccination.

  4 weeks post dose (29 days)

• Geometric Mean Concentration (GMC) of Serum Viral Protein 1 (VP1) Specific (G1.1) Immunoglobulin A (IgA) on Days 1, 8 and 29

  GMC of serum VP1 specific (G1.1) IgA was measured by Meso Scale Discovery (MSD) assay. Assay was measured in an arbitrary unit per milliliter (AU/mL).

  Days 1, 8 and 29

• GMC of Serum VP1 Specific (G2.4) IgA on Days 1, 8 and 29

  GMC of serum VP1 specific (G2.4) IgA was measured by MSD assay. Assay is measured in AU/mL.

  Days 1, 8 and 29

• Geometric Mean Fold Rise (GMFR) From Day 1 to Day 8 of Serum VP1 Specific (G1.1) IgA From Day 1 to Day 8

  GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 8 with least square mean value at baseline (Day 1).

  Day 1 to Day 8

• GMFR of Serum VP1 Specific (G1.1) IgA From Day 1 to Day 29

  GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 29 with least square mean value at baseline (Day 1).

  Day 1 to Day 29

• GMFR of Serum VP1 Specific (G2.4) IgA From Day 1 to Day 8

  GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 8 with least square mean value at baseline (Day 1).

  Day 1 to Day 8

• GMFR of Serum VP1 Specific (G2.4) IgA From Day 1 to Day 29

  GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 29 with least square mean value at baseline (Day 1).

  Day 1 to Day 29

• Number of Participants Who Achieved a 2-fold, 3-fold and 4-fold GMC Rise in Serum VP1 Specific (G1.1) IgA

  A 2, 3, 4-fold rise represented the participants with at least a 2, 3, or 4-fold rise in antibodies compared to pre-vaccination dosing Baseline (Day 1).

  Days 1, 8, 29 and 180

• Number of Participants Who Achieve a 2-fold, 3-fold and 4-fold GMC Rise in Serum VP1 Specific (G2.4) IgA

  A 2, 3, 4-fold rise represented the participants with at least a 2, 3, or 4-fold rise in antibodies compared to pre-vaccination dosing Baseline (Day 1).

  Days 1, 8, 29 and 180

• GMC of Breastmilk VP1 Specific (G1.1) IgA on Days 1, 8 and 29

  GMC of breastmilk VP1 specific (G1.1) IgA was measured by MSD assay. Assay is measured in Relative Light Unit per microgram (RLU)/µg of total IgA which is a normalized measure used to quantify the specific binding of IgA antibodies to norovirus VLPs (measured in RLU) relative to the total amount of IgA protein present in a breast milk.

  Days 1, 8, and 29

• GMC of Breastmilk VP1 Specific (G2.4) IgA on Days 1, 8 and 29

  GMC of breastmilk VP1 specific (G2.4) IgA was measured by MSD assay. Assay is measured in RLU/µg of total IgA which is a normalized measure used to quantify the specific binding of IgA antibodies to norovirus VLPs (measured in RLU) relative to the total amount of IgA protein present in a breast milk.

  Days 1, 8 and 29

• GMFR of Breastmilk VP1 Specific (G1.1) IgA From Day 1 to Day 8

  GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 8 with least square mean value at baseline (Day 1).

  Day 1 to Day 8

• GMFR of Breastmilk VP1 Specific (G2.4) IgA From Day 1 to Day 8

  GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 8 with least square mean value at baseline (Day 1).

  Day 1 to Day 8

• GMFR of Breastmilk VP1 Specific (G1.1) IgA From Day 1 to Day 29

  GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 29 with least square mean value at baseline (Day 1).

  Day 1 to Day 29

• GMFR of Breastmilk VP1 Specific (G2.4) IgA From Day 1 to Day 29

  GMFR was measured by MSD assay. The fold rise was calculated per participant by dividing the least square mean value on Day 29 with least square mean value at baseline (Day 1).

  Day 1 to Day 29

• Number of Participants Who Achieve a 2-fold, 3-fold and 4-fold GMC Rise in Breastmilk VP1 Specific (G1.1) IgA

  A 2, 3, and 4-fold rise represented the participants with at least a 2, 3, or 4-fold rise in antibody compared to pre-vaccination dosing Baseline (Day 1).

  Days 1, 8, 29, 60 and 180

• Number of Participants Who Achieve a 2-fold, 3-fold and 4-fold GMC Rise in Breastmilk VP1 Specific (G2.4) IgA

  A 2, 3, and 4-fold rise represented the participants with at least a 2, 3, or 4-fold rise in antibodies compared to pre-vaccination dosing Baseline (Day 1).

  Days 1, 8, 29, 60 and 180

Secondary Outcomes (23)

• Number of Participants With SAEs, AESIs and NOCIs Through 12 Months Post Dose

  Up to 12 months

• GMC of Serum VP1 Specific (G1.1) IgA on Day 180

  Day 180

• GMC of Serum VP1 Specific (G2.4) IgA on Day 180

  Day 180

• GMFR of Serum VP1 Specific (G1.1) IgA From Day 1 to Day 180

  Day 1 to Day 180

• GMFR of Serum VP1 Specific (G2.4) IgA From Day 1 to Day 180

  Day 1 to Day 180

Other Outcomes (19)

• GMC of Nasal VP1 Specific (G1.1) IgA

  Days 1, 8, 29, 60, and 180

• GMC of Nasal VP1 Specific (G2.4) IgA

  Days 1, 8, 29, 60, and 180

• GMFR of Nasal VP1 Specific (GI.I) IgA From Day 1 to Days 8, 29, 60 and 180

  Day 1 to Days 8, 29, 60 and 180

Study Arms (3)

Bivalent GII.4/GI.1 Medium Dose Vaccine

EXPERIMENTAL

Participants will receive a medium dose of bivalent VXA-G1.1-NN and VXA-GII.4-NS as an oral tablet on Day 1.

Biological: VXA-G1.1-NN; Biological: VXA-G2.4-NS

Bivalent GII.4/GI.1 High Dose Vaccine

EXPERIMENTAL

Participants will receive a high dose of bivalent VXA-G1.1-NN and VXA-GII.4-NS as an oral tablet on Day 1.

Biological: VXA-G1.1-NN; Biological: VXA-G2.4-NS

Placebo

PLACEBO COMPARATOR

Participants will receive matching placebo orally on Day 1.

Biological: Placebo Tablets

Interventions

VXA-G1.1-NN BIOLOGICAL

Oral tablets.

Also known as: GI.1

Bivalent GII.4/GI.1 High Dose Vaccine; Bivalent GII.4/GI.1 Medium Dose Vaccine

VXA-G2.4-NS BIOLOGICAL

Oral tablets.

Also known as: GII.4

Bivalent GII.4/GI.1 High Dose Vaccine; Bivalent GII.4/GI.1 Medium Dose Vaccine

Placebo Tablets BIOLOGICAL

Oral tablets.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Lactating females aged ≥ 18 years at the time of enrolment and their breastfed infants aged \>30 days to 11 months of age at the time of the participants' study drug administration.
• In stable and good general health, without significant medical illness, based on medical history, physical examination (including vital signs), and clinical judgment of the investigator.
• Lactating females willing and able to provide informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
• Lactating females who are willing to provide consent for their breastfed infant.
• Negative pregnancy tests at screening and prior to dose on Day 1.
• Available for all planned visits and tele-health appointments, and ability to comply with all study-related evaluations (including but not limited to having the ability and willingness to swallow multiple small enteric-coated tablets per study dose, express/pump breastmilk, and collect infant stool samples).
• Plan to continue breastfeeding as the main source of the infant's nutrition for at least 1 month (longer is preferred with goal of 6 months post dose if possible) from the time of study drug administration. Exclusive breastfeeding is acceptable but not necessary.
• The nursing infant is the product of a singleton pregnancy AND does not have any of the following:
• Any abnormality that may interfere with breastfeeding or milk absorption
• Active infection (may be included if the infection resolves and the participant is re-assessed during the screening period)
• One or more documented brief resolved unexplained events (BRUEs)
• Extreme prematurity (infants who were born at less than 28 weeks gestation)
• days of age or less at the participant's study drug administration OR greater than 11 months of age at the participant's study drug administration
• Prior hospitalization that is not exclusively for hyperbilirubinemia requiring phototherapy
• Any genetic/metabolic disease

You may not qualify if:

• Presence of a fever ≥ 38.0°C measured orally at baseline, on Day 1 prior to vaccination. (Assessment may be repeated once during screening period).
• 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 once during screening period).
• Participants who have received antipyretic/analgesic medications within 24 hours prior to the intended vaccine administration.
• Positive human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) tests at the screening visit.
• History of hypersensitivity or allergic reaction to any component of the investigational vaccine, including but not limited to fish gelatin.
• History of serious reactions to vaccination such as anaphylaxis, respiratory problems, hives, or abdominal pain.
• Presence of significant uncontrolled medical or psychiatric illness (acute or chronic) including the 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.
• History of significant pregnancy-related complications during this pregnancy, including but not limited to pre-eclampsia, eclampsia, or gestational diabetes unless a full resolution is documented.
• Cancer, or treatment for cancer, within the past 3 years (excluding fully treated and resolved basal cell carcinoma or squamous cell carcinoma).
• Presence of immunosuppression or medical condition possibly associated with impaired immune responsiveness, including diabetes mellitus type 1 or 2.
• 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. Such conditions may include but are not limited to:
• a. Any history of:
• i. Malignancy
• ii. Malabsorption
• iii. Pancreatobiliary disorders

Sponsors & Collaborators

• Vaxart: lead

Study Sites (5)

WITS RHI Research Centre

Hillbrow, 2001, South Africa

Location

Progress Clinical Research Unit

Honeydew, 2040, South Africa

Location

Newtown Clinical Research Centre

Johannesburg, 2001, South Africa

Location

Trident Clinical

Kimberley, 8301, South Africa

Location

FCRN Clinical Trials Centre (Pty) Ltd

Vereeniging, 1935, South Africa

Location

MeSH Terms

Conditions

Caliciviridae Infections

Condition Hierarchy (Ancestors)

RNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: Maria Apkarian
• Organization: Vaxart

mapkarian@vaxart.com

+1 (650) 779-4560

Study Officials

• Medical Director

  Vaxart, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: November 28, 2025
• Study Start: October 27, 2023
• Primary Completion: December 13, 2024
• Study Completion: December 13, 2024
• Last Updated: April 15, 2026
• Results First Posted: April 15, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (5)