A Trial of a Norovirus G1.1 and G2.4 Vaccine Administered Orally to Healthy Participants Aged ≥ 18 Years and ≤ 80 Years Old

NCT06944717 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: VXA-NVV-109
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to determine the safety and immunogenicity of low and high dose regimens of a next generation norovirus bivalent G1.1 and G2.4 vaccine candidate in healthy participants.

Conditions

Norovirus Infections

Keywords

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

Outcome Measures

Primary Outcomes (15)

• Number of Participants Experiencing Solicited Symptoms of Reactogenicity (Gastrointestinal and Systemic) for 1 Week Following Study Intervention Dose

  7 days

• Duration of Solicited Symptoms of Reactogenicity (Gastrointestinal and Systemic) for 1 Week Following Study Intervention Dose

  Approximately 1 year

• Severity of Solicited Symptoms of Reactogenicity (Gastrointestinal and Systemic) for 1 Week Following Study Intervention Dose

  7 days

• Number of Participants Experiencing Unsolicited Adverse Events (AE) for 28 Days Following the Study Intervention Dose

  28 days

• Number of Participants Experiencing Unsolicited New Onset of Chronic Illness (NOCI) for 28 Days Following the Study Intervention Dose

  28 days

• Duration of Unsolicited AEs for 28 Days Following the Study Intervention Dose

  Approximately 1 year

• Duration of Unsolicited NOCIs for 28 Days Following the Study Intervention Dose

  Approximately 1 year

• Severity of Unsolicited AEs for 28 Days Following the Study Intervention Dose

  28 days

• Severity of Unsolicited NOCIs for 28 Days Following the Study Intervention Dose

  28 days

• Geometric Mean Titer (GMT) at Day 0 of Serum Functional Antibody Against GI.1 Measured by Norovirus Blocking Antibody Assay (NBAA)

  Day 0

• GMT at Day 28 of Serum Functional Antibody Against GI.1 Measured by NBAA

  Day 28

• GMT at Day 0 of Serum Functional Antibody Against GII.4 Measured by NBAA

  Day 0

• GMT at Day 28 of Serum Functional Antibody Against GII.4 Measured by NBAA

  Day 28

• Geometric Mean Fold Rise (GMFR) from Day 0 to Day 28 of Serum Functional Antibody Against GI.1 Measured by NBAA

  From Day 0 to Day 28

• GMFR from Day 0 to Day 28 of Serum Functional Antibody Against GII.4 Measured by NBAA

  From Day 0 to Day 28

Study Arms (3)

Bivalent Low Dose Next Generation Vaccine

EXPERIMENTAL

Healthy participants will receive Norovirus GI.1 Norwalk VP1 Vaccine, Modified Oral E1-/E3-Deleted Replication Defective Recombinant Adenovirus 5 with dsRNA Adjuvant (VXA-G1.1-NN-T) (1x10\^10 infectious units (IU)) and Norovirus GII.4 Sydney VP1 Vaccine, Modified Oral E1-/E3-Deleted Replication Defective Recombinant Adenovirus 5 with dsRNA Adjuvant (VXA-G2.4-NS-T) (1x10\^10 IU) orally.

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

Bivalent High Dose Legacy Vaccine

EXPERIMENTAL

Healthy participants will receive Norovirus GI.1 Norwalk Vaccine Protein 1 (VP1) Vaccine, Oral E1-/E3-Deleted Replication Defective Recombinant Adenovirus 5 with double-stranded ribonucleic acid (dsRNA) Adjuvant (VXA-G1.1-NN) (1x10\^11 IU) and Norovirus GII.4 Sydney VP1 Vaccine, Oral E1-/E3-Deleted Replication Defective Recombinant Adenovirus 5 with dsRNA Adjuvant (VXA-G2.4-NS) (1x10\^11 IU) orally.

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

Bivalent High Dose Next Generation Vaccine

EXPERIMENTAL

Healthy participants will receive VXA-G1.1-NN-T (1x10\^11 IU) and VXA-G2.4-NS-T (1x10\^11 IU) orally. A sentinel group will be enrolled, if there is positive recommendation from the safety monitoring committee, enrollment will continue in this arm.

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

Interventions

VXA-G1.1-NN BIOLOGICAL

Legacy vaccine, administered orally.

Bivalent High Dose Legacy Vaccine

VXA-G2.4-NS BIOLOGICAL

Legacy vaccine, administered orally.

Bivalent High Dose Legacy Vaccine

VXA G1.1 NN-T BIOLOGICAL

Next generation vaccine, administered orally.

Bivalent High Dose Next Generation Vaccine; Bivalent Low Dose Next Generation Vaccine

VXA G2.4 NS-T BIOLOGICAL

Next generation vaccine, administered orally.

Bivalent High Dose Next Generation Vaccine; Bivalent Low Dose Next Generation Vaccine

Eligibility Criteria

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

You may qualify if:

• ≥ 18 and ≤ 80 years old at the time of signing the Informed Consent Form (ICF).
• In stable and good general health and without significant medical illness (based on review of medical history, physical examination, current health status, and vital signs at Screening) as determined by the Investigator, with Screening lab values within normal limits or abnormalities assessed as not clinically significant.
• Body mass index (BMI) \> 17.0 and \< 35.0 kg/m\^2 at Screening.
• Available for all planned visits and tele-health appointments, and willing to complete all Protocol-defined procedures and assessments (including ability and willingness to swallow multiple small enteric-coated tablets per study dose).
• Male or female participants.
• Female participants must not be breastfeeding and must provide a negative pregnancy test at Screening and pre-dose on Day 0.
• Female participants must fulfill at least one of the following criteria:
• At least 1 year post-menopausal (defined as amenorrhea for ≥ 12 consecutive months prior to Screening without alternative medical cause) or surgically sterile (hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal occlusion/ligation).
• Female participants of childbearing potential must be willing to use a highly effective form of contraception for 30 days prior to study drug administration and until 60 days after study drug administration. Acceptable forms are oral, implantable, intrauterine, transdermal, intravaginal, injectable, double barrier or abstinence (participants using diaphragms must also use condoms). The Investigator must approve the form of contraception. Female participants must also refrain from egg donation for the 1 month prior to dosing through 60 days post-vaccination.
• Male participants must fulfill one of the following criteria:
• Male participants must agree to refrain from donating sperm and practice abstinence from all intercourse or use an effective method of birth control which includes condom use from study drug administration to 90 days post-dose.
• At least 1 year post-vasectomy and have confirmed that they have obtained documentation of the absence of sperm in the ejaculate.
• 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:

• 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, asplenia, and functional asplenia.
• 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:
• Any history of:
• Gastrointestinal malignancy
• Masabsorption
• Pancreato-biliary disorders
• Inflammatory bowel disease
• Irritable bowel disease
• Hiatal hernia
• Surgical resection
• History of diagnosis or treatment in past 5 years of:
• Osophageal or gastric motility disorder
• Gastro esophageal reflux disorder if any of the following is met:

Sponsors & Collaborators

• Vaxart: lead

Study Sites (1)

Johnson County Clin Trials - JCCT

Lenexa, Kansas, 66219, United States

Location

MeSH Terms

Conditions

Caliciviridae Infections

Condition Hierarchy (Ancestors)

RNA Virus Infections; Virus Diseases; Infections

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2025
• First Posted: April 25, 2025
• Study Start: March 3, 2025
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: April 29, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)