NCT02473224

Optimal Human Dose for GII.2 Norovirus (Snow Mountain) Challenge Studies

Phase I Study to Determine the Optimal Human Dose for GII.2 Norovirus (Snow Mountain) Challenge Studies

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 44 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 49 Years
• Healthy volunteers: Accepted

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.

Conditions

• Gastroenteritis Norovirus

Interventions

Type	Name	Description
BIOLOGICAL	Norovirus GII.2 Challenge	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
OTHER	Placebo	Placebo: 80 ml of sterile water for oral administration

Timeline

• Start date: 2015-10-28
• Primary completion: 2018-11-27
• Completion: 2018-11-27
• First posted: 2015-06-16
• Last updated: 2018-12-07

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study