Phase I Norovirus Challenge Model
Condition: Gastroenteritis Norovirus
MeSH terms: Gastroenteritis
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a safety and infectivity study of experimental human Norovirus genogroup GII.4
      administered to 48 healthy non-pregnant adults, 18-49 years of age, negative for COVID-19 by
      antigen testing at the time of norovirus challenge. Subjects will be admitted to the Vaccine
      Research Center inpatient facility and challenged with a dose of human norovirus GII.4
      challenge strain. The challenge study will be conducted in 3 cohorts of approximately 16
      subjects each, 15 subjects will have a functional FUT-2 gene (secretor positive) and 1
      subject will have a non-functional FUT-2 gene (non-secretor). Subjects in Cohort 1 will
      receive 3.5x10^3 copies of norovirus, in Cohort 2 will receive 3.5x10^4 copies of norovirus
      and in Cohort 3 will receive 3.5x10^5 copies of norovirus. Based on the illness rate of
      subjects meeting the primary outcome measure in secretor - positive subjects of the initial
      cohort, the decision will be made with regards to dosing of the second and the third cohorts.
      Study duration is approximately 12-18 months with subject participation duration of 6-8
      months. The primary objective of this study is to determine the optimal challenge dose of
      Norovirus GII.4 CIN-3 Batch No.: 01-16C3 to achieve illness in > / = 50% of subjects (illness
      is defined as norovirus infection determined by positive Polymerase Chain Reaction (PCR) and
      either: a) > / = 3 loose or liquid stools, in a 24-hour period, b) > / = 300 gm of loose or
      liquid stool in a 24-hour period or c) and/or any episode of vomiting), during the inpatient
      period.
    

Detailed description: 
      This is a double-blind, safety and infectivity study of experimental human Norovirus
      genogroup GII.4 administered to 48 healthy non-pregnant adults, 18-49 years of age, negative
      for COVID-19 by antigen testing at the time of norovirus challenge. Subjects will be admitted
      to the Vaccine Research Center inpatient facility and challenged with a dose of human
      norovirus GII.4 challenge strain. The challenge study will be conducted in 3 cohorts of
      approximately 16 subjects each, 15 subjects will have a functional FUT-2 gene (secretor
      positive) and 1 subject will have a non-functional FUT-2 gene (non-secretor). Subjects in
      Cohort 1 will receive 3.5x10^3 copies of norovirus, in Cohort 2 will receive 3.5x10^4 copies
      of norovirus and in Cohort 3 will receive 3.5x10^5 copies of norovirus. Based on the illness
      rate of subjects meeting the primary outcome measure in secretor - positive subjects of the
      initial cohort, the decision will be made with regards to dosing of the second and the third
      cohorts. Subjects will remain in the inpatient facility for at least four days following the
      challenge and assessed daily for clinical and virologic evidence of norovirus infection.
      After the discharge, subjects will return to the site for evaluation on Days 6, 15, 30, 45,
      and 60 post challenge. A final phone call will be performed at day 180 to obtain an interim
      medical history. Study duration is approximately 12-18 months with subject participation
      duration of 6-8 months. The primary objective of this study is to determine the optimal
      challenge dose of Norovirus GII.4 CIN-3 Batch No.: 01-16C3 to achieve illness in > / = 50% of
      subjects (illness is defined as norovirus infection determined by positive Polymerase Chain
      Reaction (PCR) and either: a) > / = 3 loose or liquid stools, in a 24-hour period, b) > / =
      300 gm of loose or liquid stool in a 24-hour period or c) and/or any episode of vomiting),
      during the inpatient period. The secondary objectives are: 1) To evaluate the safety of the
      Norovirus GII.4 CIN-3 Batch No.: 01-16C3 challenge strain; 2) To determine the rate of
      infection at different challenge doses by detection of norovirus GII.4 in the stool using
      specific qRT-PCR and Anti-norovirus GII.4 serum IgG by Enzyme-Linked Immunnosorbent Assay
      (ELISA) (> / = 4-fold rise from baseline through Day 30); 3) To measure the severity of acute
      gastroenteritis; 4) To determine the quantity and duration of virus shedding in stool by
      qRT-PCR.
    

Intervention name(s): Norovirus GII.4 Challenge Pool
Intervention type(s): Biological
Intervention description(s): Subjects will be NPO (nothing by mouth) for at least 90 minutes followed by ingestion of 60 mL of a 2% sodium bicarbonate solution by mouth. 2 minutes later, subjects will be administered Norovirus GII.4 CIN-3. Five minutes following administration of the challenge dose, subjects will be administered a 60 mL volume of a 2% sodium bicarbonate solution and then remain NPO for at least the next 90 minutes. Subjects will be observed during the 60 minutes after receipt of the challenge by a study team member to detect and treat any immediate adverse reactions.
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Healthy Adults; Norovirus GII.4 CIN-3; Optimal Human Challenge Dose