A Study to Determine the Safety and Immunogenicity of Bivalent GI.1 and GII.4 Vaccines in Healthy Volunteers

NCT05626803 | Completed Phase 2 Results FDA Drug

• 1 other identifier: VXA-NVV-202
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 3

Brief Summary

This study is designed to evaluate the safety and immunogenicity of two monovalent Norovirus (NoV) oral tableted vaccine candidates, VXA-G1.1-NN and VXA-GII.4-NS co-administered (bivalent delivery) against a matching placebo arm. Bivalent GI.1 and GII.4 vaccines are being investigated for the prevention of noroviral gastroenteritis caused by norovirus GI.1 and GII.4.

Conditions

Norovirus Infections

Outcome Measures

Primary Outcomes (14)

• Number of Participants With Solicited Symptoms of Reactogenicity (Gastrointestinal [GI] and Systemic)

  Solicited adverse events (AEs) are predefined signs and symptoms of reactogenicity for which the participants were specifically questioned, and which were noted by the participant in their Solicited Symptom Diary for 7 days after drug administration, including: * fever (any temperature 100.4°F or higher) * headache * myalgia (muscle pain) * abdominal pain * anorexia (defined as not eating) * nausea * vomiting * diarrhoea * malaise/fatigue. The severity of each solicited symptoms of reactogenicity was graded by the participant as mild, moderate, severe or life-threatening. Participants with multiple Solicited AEs were only counted once in summarizing overall percentages of Solicited AEs, the highest severity of which was used.

  Up to Day 8

• Number of Participants With Unsolicited AEs

  Treatment emergent AEs (TEAEs) are defined as AEs that occurred following the first administration of study medication. An unsolicited AE is an observed AE that did not fulfill the conditions prelisted in terms of diagnosis and/or onset window post-vaccination. The severity of each AE was graded by the participant as mild, moderate or severe/ life-threatening.

  Up to Day 29

• Serum - Anti-Vaccine Protein 1 (VP1) GI.1 Immunoglobulin A (IgA) Levels by Meso Scale Discovery (MSD) Assay

  Serum levels of Anti-VP1 GI.1 IgA were evaluated using cellular and humoral immune (HI) function assays from blood and mucosal (saliva and nasal swab) samples. 95% confidence intervals were estimated by Clopper-Pearson exact method. Assay is measured in AU/mL.

  Day 1 and Day 29

• Fold Rise in Serum - Anti-VP1 GI.1 IgA Levels by MSD Assay

  Serum levels of Anti-VP1 GI.1 IgA were evaluated using cellular and HI function assays from blood and mucosal (saliva and nasal swab) samples. The fold rise was calculated per participant by dividing the antibody concentration (original scale) on Day 29 with antibody concentration at baseline (Day 1). 95% confidence intervals were estimated by Clopper-Pearson exact method.

  Day 1 and Day 29

• Serum - Anti-VP1 GII.4 IgGA Levels by MSD Assay

  Serum levels of Anti-VP1 GII.4 IgA were evaluated using cellular and HI function assays from blood and mucosal (saliva and nasal swab) samples. 95% confidence intervals were estimated by Clopper-Pearson exact method. Assay is measured in AU/mL.

  Day 1 and Day 29

• Fold Rise in Serum - Anti-VP1 GII.4 IgA Levels by MSD Assay

  Serum levels of Anti-VP1 GII.4 IgA were evaluated using cellular and HI function assays from blood and mucosal (saliva and nasal swab) samples. The fold rise was calculated per participant by dividing the antibody concentration (original scale) on Day 29 with antibody concentration at baseline (Day 1). 95% confidence intervals were estimated by Clopper-Pearson exact method.

  Day 1 and Day 29

• Serum - Anti-VP1 GI.1 Immunoglobulin G (IgG) Levels by MSD Assay

  Serum levels of Anti-VP1 GI.1 IgG were evaluated using cellular and HI function assays from blood and mucosal (saliva and nasal swab) samples. 95% confidence intervals were estimated by Clopper-Pearson exact method. Assay is measured in AU/mL.

  Day 1 and Day 29

• Fold Rise in Serum - Anti-VP1 GI.1 IgG Levels by MSD Assay

  Serum levels of Anti-VP1 GI.1 IgG were evaluated using cellular and HI function assays from blood and mucosal (saliva and nasal swab) samples. The fold rise was calculated per participant by dividing the antibody concentration (original scale) on Day 29 with antibody concentration at baseline (Day 1). 95% confidence intervals were estimated by Clopper-Pearson exact method.

  Day 1 and Day 29

• Serum - Anti-VP1 GII.4 IgG Levels by MSD Assay

  Serum levels of Anti-VP1 GII.4 IgG were evaluated using cellular and HI function assays from blood and mucosal (saliva and nasal swab) samples. 95% confidence intervals were estimated by Clopper-Pearson exact method. Assay is measured in AU/mL.

  Day 1 and Day 29

• Fold Rise in Serum - Anti-VP1 GII.4 IgG Levels by MSD Assay

  Serum levels of Anti-VP1 GII.4 IgG were evaluated using cellular and HI function assays from blood and mucosal (saliva and nasal swab) samples. The fold rise was calculated per participant by dividing the antibody concentration (original scale) on Day 29 with antibody concentration at baseline (Day 1). 95% confidence intervals were estimated by Clopper-Pearson exact method.

  Day 1 and Day 29

• Serum - Anti-VP1 GI.1 Blocking Antibodies (BT50) Titers by MSD Assay

  Serum levels of Anti-VP1 GI.1 BT50 were evaluated using cellular and HI function assays from blood and mucosal (saliva and nasal swab) samples. 95% confidence intervals were estimated by Clopper-Pearson exact method.

  Day 1 and Day 29

• Fold Rise in Serum - Anti-VP1 GI.1 BT50 Titers by MSD Assay

  Serum levels of Anti-VP1 GI.1 BT50 were evaluated using cellular and HI function assays from blood and mucosal (saliva and nasal swab) samples. The fold rise was calculated per participant by dividing the antibody concentration (original scale) on Day 29 with antibody concentration at baseline (Day 1).

  Day 1 and Day 29

• Serum - Anti-VP1 GII.4 BT50 Titers by MSD Assay

  Serum levels of Anti-VP1 GII.4 BT50 were evaluated using cellular and HI function assays from blood and mucosal (saliva and nasal swab) samples. 95% confidence intervals were estimated by Clopper-Pearson exact method.

  Day 1 and Day 29

• Fold Rise in Serum - Anti-VP1 GII.4 BT50 Titers by MSD Assay

  Serum levels of Anti-VP1 GII.4 BT50 were evaluated using cellular and HI function assays from blood and mucosal (saliva and nasal swab) samples. The fold rise was calculated per participant by dividing the antibody concentration (original scale) on Day 29 with antibody concentration at baseline (Day 1). 95% confidence intervals were estimated by Clopper-Pearson exact method.

  Day 1 and Day 29

Study Arms (4)

Open Label Sentinel

EXPERIMENTAL

Bivalent GII.4/GI.1 vaccine Bivalent GII.4/GI.1 high dose vaccine (VXA-GII.4-NS plus VXA-G1.1-NN) 1×10 to the power 11 tablets total dose is 2×10 to the power 11 IU/dose (sentinel n=10)

Drug: Open label Bivalent GII.4/GI.1 high dose vaccine 2×10 to the power 11 IU/dose

Medium Dose Arm

EXPERIMENTAL

Bivalent GII.4/GI.1 vaccine Bivalent GII.4/GI.1 medium dose vaccine (VXA-GII.4-NS plus VXA-G1.1-NN) 5×10 to the power 10 tablets total dose is 1×10 to the power 11 IU/dose (N=50)

Drug: Bivalent GII.4/GI.1 medium dose vaccine 1×10 to the power 11 IU/dose

High Dose Arm

EXPERIMENTAL

Bivalent GII.4/GI.1 vaccine Bivalent GII.4/GI.1 high dose vaccine (VXA-GII.4-NS plus VXA-G1.1-NN) 1×10 to the power 11 tablets total dose is 2×10 to the power 11 IU/dose (N=50)

Drug: Bivalent GII.4/GI.1 high dose vaccine 2×10 to the power 11 IU/dose

Placebo Arm

PLACEBO COMPARATOR

Placebo tablets (N= 25)

Drug: Placebo

Interventions

Open label Bivalent GII.4/GI.1 high dose vaccine 2×10 to the power 11 IU/dose DRUG

The first 10 sentinel subjects will receive open label high dose of active vaccine. Bivalent GII.4/GI.1 high dose vaccine (VXA-GII.4-NS plus VXA-G1.1-NN) 1×10 to the power 11 tablets; total dose is 2×10 to the power 11 IU/dose

Open Label Sentinel

Bivalent GII.4/GI.1 high dose vaccine 2×10 to the power 11 IU/dose DRUG

50 subjects will receive high dose of active vaccine. Bivalent GII.4/GI.1 high dose vaccine (VXA-GII.4-NS plus VXA-G1.1-NN) 1×10 to the power 11 tablets; total dose is 2×10 to the power 11 IU/dose

High Dose Arm

Bivalent GII.4/GI.1 medium dose vaccine 1×10 to the power 11 IU/dose DRUG

50 subjects will receive Bivalent GII.4/GI.1 medium dose vaccine (VXA-GII.4-NS plus VXA-G1.1-NN) 5×10 to the power 10 tablets; total dose is 1×10 to the power 11 IU/dose

Medium Dose Arm

Placebo DRUG

25 subjects will receive matching placebo

Placebo Arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible for this study, subjects must meet all the following:
• In stable and good general health, without significant medical illness, based on medical history, physical examination, and vital signs at screening based on investigator judgement.
• Body mass index (BMI) between \>/= 17.0 and \</= 35.0 kg/m2 at screening SNG.
• Available for all planned visits and tele-health appointment, and willing to complete all protocol-defined procedures and assessments (including ability and willingness to swallow multiple small enteric-coated tablets per study dose).
• Female subjects must not be breastfeeding and must provide a negative pregnancy test at screening and pre-dose.
• Female subjects must fulfill one of the following criteria:
• i. At least 1 year post-menopausal (defined as amenorrhea for greater than or equal to 12 consecutive months prior to screening without alternative medical cause) or surgically sterile.
• ii. Female subjects of childbearing potential must be willing to use a highly effective form of contraception for 30 days prior to initial vaccination and until 60 days after last vaccination. Acceptable forms are oral, implantable, intrauterine, transdermal, intravaginal, injectable, double barrier or abstinence (subjects using diaphragms must also use condom). The form of contraception must be approved by the investigator.
• iii. Male subjects must agree to practice abstinence from heterosexual intercourse or to use an effective method of birth control as noted above from first vaccination to 60 days after last vaccination. Male subjects must agree to refrain from donating sperm and practice abstinence from all intercourse or to use an effective method of double barrier birth control or condom as noted above from first vaccination to 60 days after last vaccination.
• Capable of understanding and giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in the protocol.

You may not qualify if:

• The subjects must be excluded from participating in the study if they meet any of the following:
• Known clotting/bleeding issues and/or personal and family history with increased risk of bleeding or clotting.
• 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 prior to screening and reconfirmed at baseline.
• Cancer, or treatment for cancer or any procedure or preventive medication for cancer or to prevent recurrence, within 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 and 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. GI malignancy ii. malabsorption iii. pancreatobiliary disorders iv. inflammatory bowel disease v. irritable bowel disease vi. hiatal hernia vii. surgical resection b. History of diagnosis or treatment in past 5 years of: i. esophageal or gastric motility disorder ii. gastro esophageal reflux disorder iii. peptic ulcer iv. cholecystectomy
• 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 once during Screening Period)
• Presence of a fever greater than or equal to 38°C measured orally at baseline.
• Any significant hospitalization within the last year which in the opinion of the investigator or sponsor could interfere with study participation.
• Any history or conditions that may lead to higher risk of clotting events and/or thrombocytopenia:

Sponsors & Collaborators

• Vaxart: lead

Study Sites (3)

Ark Clinical Research

Long Beach, California, 90806, United States

Location

Johnson County Clin-Trials

Lenexa, Kansas, 66219, United States

Location

Nucleus Network Pty Ltd

Saint Paul, Minnesota, 55114, United States

Location

MeSH Terms

Conditions

Caliciviridae Infections

Condition Hierarchy (Ancestors)

RNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: Melanie Drayton
• Organization: Vaxart

ClinicalTrials@Vaxart.com

650-392-3109

Study Officials

• James Cummings, MD

  Vaxart, Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2022
• First Posted: November 25, 2022
• Study Start: January 26, 2023
• Primary Completion: October 16, 2023
• Study Completion: October 16, 2023
• Last Updated: April 15, 2025
• Results First Posted: April 15, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)