Optimal Human Dose for GII.2 Norovirus (Snow Mountain) Challenge Studies
Condition: Gastroenteritis Norovirus
MeSH terms: Gastroenteritis
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a phase I, randomized, double blind, as well as partially blinded (for Cohort 4),
      placebo-controlled safety, illness, and infection study of a new experimental human challenge
      stock of the Norovirus genogroup II, genotype 2 (GII.2) isolate designated Snow Mountain
      virus (SMV). The study duration is 24 - 36 months. The primary objectives are to: 1) evaluate
      the safety and reactogenicity of the GII.2 Snow Mountain norovirus challenge stock and 2)
      determine a safe and optimal challenge dose of GII.2 Snow Mountain norovirus to achieve
      illness in a high proportion (= / > 75%) of subjects.
    

Detailed description: 
      This is a phase I, randomized, double blind, as well as partially blinded (for Cohort 4),
      placebo-controlled safety, illness, and infection study of a new experimental human challenge
      stock of the Norovirus genogroup II, genotype 2 (GII.2) isolate designated Snow Mountain
      virus (SMV), administered to healthy adults 18-49 years of age. Groups of 11 subjects each
      will be admitted to the inpatient hospital research unit, challenged with live SMV or placebo
      by oral administration, and remain in isolation in the unit for at least 4 days following
      challenge. The study duration is 24 - 36 months. Subjects will be followed post-challenge for
      safety, reactogenicity, and illness (primary objectives), and secondary or exploratory
      objectives including infection and immune responses. There will be multiple clinical
      assessments and collection of blood, emesis, saliva, and stool specimens. The primary
      objectives are to: 1) evaluate the safety and reactogenicity of the GII.2 Snow Mountain
      norovirus challenge stock and 2) determine a safe and optimal challenge dose of GII.2 Snow
      Mountain norovirus to achieve illness in a high proportion (= / > 75%) of subjects. The
      secondary objectives are to: 1) determine the rate of infection in study participants after
      norovirus GII.2 challenge, 2) determine the quantity and duration of virus shedding in stool
      by RT-qPCR, 3) estimate the median time to cessation of shedding, 4) determine the modified
      Vesikari score as a measure of gastroenteritis severity, 5) determine GII.2 Snow Mountain
      norovirus-specific Immunoglobulin titers by ELISA before and after the challenge, 6)
      determine the effect of pre-existing GII.2 Snow Mountain norovirus-specific immunoglobulin in
      serum and saliva on the rate of infection, 7) determine total and GII.2 Snow Mountain
      norovirus-specific IgA- and IgG-Secreting Cells in circulation by ELISpot assay, 8) once the
      optimal challenge dose is determined in secretor positive subjects: investigate the safety
      and illness rate using that dose of the GII.2 challenge stock in secretor negative subjects.
    

Intervention name(s): Norovirus GII.2 Challenge; Placebo
Intervention type(s): Biological; Other
Intervention description(s): GII.2 Snow Mountain Norovirus Filtrate. Cohort 1: 1.2x10^4 Genome Equivalent Copies (GEC) oral dose on Day 1. Cohort 2: either 1.2 x 10^2 GEC or 1.2 x10^6 GEC oral dose on Day 1, depending on the results of prior Cohort 1. Cohort 3: either 1GEC, 1.2 x 10^1 GEC, 1.2 x 10^2 GEC, 1.2 x 10^3 GEC, 1.2 x 10^5 GEC, or 1.2 x 10^6 GEC, or 1.2 GEC x 10^7 oral dose on Day 1, depending on the percentage of subjects with illness from Cohorts 1 and 2. Cohort 4: optimal dose of GEC as determined by the results of cohorts 1-3; Placebo: 80 ml of sterile water for oral administration
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Other
Keywords: challenge; GII.2; HID50; Norovirus; Snow Mountain filtrate