Norovirus Challenge Study
Condition: Norovirus Infections
MeSH terms: Caliciviridae Infections
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Detailed description: 
      Study Population Healthy male and female adult volunteers age 18 to 49 years inclusive with
      blood type O or A and who are confirmed H type-1 antigen secretory positive Investigational
      Product

      Active Vaccine:

        -  Norovirus GI.1 Norwalk VP1 Vaccine (VXA-G1.1-NN), an Oral E1/E3-Deleted
           Replication-Defective Recombinant Adenovirus serotype 5 with double-stranded ribonucleic
           acid (dsRNA) Adjuvant. The vaccine vector encodes for a full-length VP1 gene from
           Norwalk virus (NV). The adjuvant is a short hairpin RNA, expressed as a 21 nucleotide
           sequence (GAAACGA TATGGGCTGAATAC) as a tandem sequence in forward and reverse
           orientations separated by 6 nucleotides that comprise the loop of the RNA. The final
           drug product (DP) is formulated into enteric-coated tablet.

        -  Dose: 1x10E11 IU±0.5 log

      Placebo Control:

      • Oral tablets similar in appearance and number to active vaccine tablets Multiple tablets of
      study drug will be dispensed to allow delivery of the intended vaccine dose (1x10E11 IU). A
      matching number of placebo tablets will be dispensed to maintain the study blinding.

      Viral Challenge Inoculum

        -  Norovirus GI.1 (Norwalk Virus Inoculum Lot 001-09NV, IND 14697)

        -  Dose: 1x10E6 Genomic Copies (GC). A dose which allows 50% - 65% infectivity in the
           healthy adult population (per NV infection rate observed in the GI.1 viral titration
           study

      Study Hypothesis Norovirus vaccine (VXA-G1.1-NN) will protect against Norovirus
      Gastroenteritis (NVG) related to norovirus (NoV) infection in the challenge model

      Approximately 120 subjects will be dosed in the vaccination phase to ensure at least 100
      subjects (~ 50 VXA-G1.1-NN vaccine and 50 placebo) are available to participate in the
      challenge phase. 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. NV illness lasts 2-4 days and is self-limited. 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.

      The following study visits and remote contacts will be conducted during the study

      Vaccination Phase:

        -  Pre-Screening Period (Days -90 to Screening) may be utilized for purposes of
           ascertaining subjects' H type-1 antigen secretory status and blood type

        -  Screening Period (Days -45 to -1)

        -  Day 1 Visit (Baseline assessments; day of randomization and vaccination)

        -  Day 8 Visit (safety and evaluation of immune response)

        -  Day 28 (evaluation of immune response; 1 day prior to challenge, start inpatient stay)

      Challenge Phase:

        -  Day 29 (viral challenge, sequestration)

        -  Days 30 to 33 (sequestration - discharge; +3 days)

        -  Day 36 Visit (evaluation of immune response and safety assessment)

        -  Day 57 Visit (end of active period)

      Safety Follow-Up:

        -  Day 120, Day 180, Day 240 and Day 300 (follow-up contact)

        -  Day 365 (follow-up phone call): Study completion

      An independent Safety Monitoring Committee (SMC) will convene at pre-defined intervals during
      the norovirus challenge period, and also ad hoc as needed during the vaccination and
      challenge periods, to oversee the safety of the study.
    

Intervention name(s): VXA-G1.1-NN; Placebo Tablets; Norovirus GI.1 Norwalk Virus Inoculum
Intervention type(s): Biological; Other; Biological
Intervention description(s): Norovirus GI.1 Norwalk VP1 Vaccine, Oral E1-/E3-Deleted Replication Defective Recombinant Adenovirus 5 with dsRNA Adjuvant; Oral tablets similar in appearance and number to active vaccine tablets; Norwalk Virus Inoculum Lot 01-09NV
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Single (Participant)
Primary purpose: Prevention