Norovirus Challenge Study

NCT05212168 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: VXA-NVV-201
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 1

Brief Summary

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.

• Arm 1: VXA-G1.1-NN oral vaccine tablets \[1x1011 IU±0.5 log\]
• Arm 2: Placebo tablets similar in appearance and number to active vaccine tablets 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.

Conditions

Norovirus Infections

Outcome Measures

Primary Outcomes (5)

• 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: 1. nausea 2. fever (oral temperature ≥ 37.6°C) 3. abdominal cramps or pains 4. abdominal gurgling or bloating 5. myalgia NV infection was defined as having 1 or more positive results in stool or urine by quantitative real time reverse transcription polymerase chain reaction (qRT-PCR).

  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

  Blood samples were collected at different timepoints throughout the study.

  Day 28

Secondary Outcomes (13)

• Number of Participants Who Experienced Solicited Symptoms of Reactogenicity

  Up to Day 8

• Number of Participants Who Experienced Unsolicited Adverse Events (AEs) During the Vaccination Phase

  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)

  Up to approximately 12 months post vaccination

• Number of Participants Who Experienced Unsolicited AEs During the Challenge Phase

  Up to Day 29 of Challenge Phase (28-days phase)

• Number of Participants With AGE During the Inpatient Challenge Phase

  Day 28 of Challenge Phase (28-days phase)

Other Outcomes (2)

• VP1 GI.1-specific Fecal IgA at Day 1, Day 28 and Day 57

  Day 1 (baseline), Day 28 and Day 57

• VP1 GI.1-specific Saliva IgA at Day 1, Day 28 and Day 57

  Day 1 (baseline), Day 28 and Day 57

Study Arms (2)

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

Biological: VXA-G1.1-NN; Biological: Norovirus GI.1 Norwalk Virus Inoculum

Placebo Arm

PLACEBO COMPARATOR

Subject receiving Placebo oral tablets similar in appearance and number to active vaccine tablets

Other: Placebo Tablets; Biological: Norovirus GI.1 Norwalk Virus Inoculum

Interventions

VXA-G1.1-NN BIOLOGICAL

Norovirus GI.1 Norwalk VP1 Vaccine, Oral E1-/E3-Deleted Replication Defective Recombinant Adenovirus 5 with dsRNA Adjuvant

Active Vaccine Arm

Placebo Tablets OTHER

Oral tablets similar in appearance and number to active vaccine tablets

Placebo Arm

Norovirus GI.1 Norwalk Virus Inoculum BIOLOGICAL

Norwalk Virus Inoculum Lot 01-09NV

Active Vaccine Arm; Placebo Arm

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• At least one year post-menopausal;
• Surgically sterile;
• Use of oral, implantable, transdermal or injectable contraceptives for 30 days prior to immunization and until 60 days after challenge;
• 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)

You may not qualify if:

• 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:
• 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 one of the following ECG findings within 45 days prior to vaccination:

Sponsors & Collaborators

• Vaxart: lead

Study Sites (1)

AltaSciences LA

Cypress, California, 90630, United States

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

• James Cummings, MD

  Vaxart, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2022
• First Posted: January 27, 2022
• Study Start: December 27, 2021
• Primary Completion: April 13, 2023
• Study Completion: October 27, 2023
• Last Updated: November 5, 2025
• Results First Posted: May 6, 2025

Record last verified: 2025-09

Locations

US (1)