Gastroenteritis Norovirus Clinical Trial
Official title:
Phase I Study to Determine the Optimal Human Challenge Dose for a Norovirus GII.4 Challenge Stock (CIN-1)
This is phase I, double blind, placebo-controlled safety and infectivity study of experimental human Norovirus genogroup GII.4 administered to healthy adults 18-49 years of age. Subjects susceptible to the human norovirus GII.4 challenge strain. The challenge study will be conducted in 2-3 cohorts of approximately 20 subjects each.Subjects will remain in the inpatient facility for at least four days following challenge and assessed daily for clinical and virologic evidence of norovirus infection. The primary objectives are to evaluate the safety and reactogenicity of the norovirus GII.4 (CIN-1; 031693) challenge stock and to determine a safe and optimal challenge dose of Norovirus GII.4 Challenge Stock norovirus to achieve illness in > /=50% of subjects. Illness is defined as: diarrhea (>3 loose or liquid stools or >300 gm of loose or liquid stool /24h), and/or vomiting during the inpatient period, in a participant with evidence of infection.
This is phase I, double blind, placebo-controlled safety and infectivity study of
experimental human Norovirus genogroup GII.4 administered to healthy adults 18-49 years of
age. The unblinded pharmacist will assign treatments. Subjects will be admitted to an
inpatient nursing unit, challenged with live GII.4 Norovirus strain by oral administration,
remain in the unit for at least 4 days following challenge and then followed for
post-challenge safety and efficacy with multiple clinical assessments and collection of
blood and stool specimens.
Subjects susceptible to the human norovirus GII.4 challenge strain, CIN-1 (i.e. presence of
a functional FUT-2 gene), regardless of ABO blood type, will be housed in the Cincinnati
Center for Clinical Research (CCCR) inpatient facility and challenged orally with different
doses of the virus. The challenge study will be conducted in 2-3 cohorts of approximately 20
subjects each, with the initial cohort receiving 103 RT-PCR units or placebo (9 "challenge"
and 1 "placebo" per 10 subjects). Based on the illness rate of acute gastroenteritis (AGE)
in the initial cohort, the second cohort will be enrolled to receive a challenge dose based
on the results of the previous studies. Additional cohorts may be necessary. Illness is
defined as infection accompanied by vomiting and/or diarrhea during the inpatient stay.Two
to three additional subjects per cohort will serve as alternates in the event that any of
the study subjects are unavailable or become ineligible at the time of the inpatient
study.Subjects will remain in the inpatient facility for at least four days following
challenge and assessed daily for clinical and virologic evidence of norovirus infection.
Subjects will return to the investigational site for evaluation on Day 6 (6-8 days) and
about 15 (14-16 days) and 30 days (28-35 days), and 45 (40-45 days), and (55-65) post
challenge.
The primary objectives are to evaluate the safety and reactogenicity of the norovirus GII.4
(CIN-1; 031693) challenge stock and to determine a safe and optimal challenge dose of
Norovirus GII.4 Challenge Stock norovirus to achieve illness in > /=50% of subjects. Illness
is defined as: diarrhea (>3 loose or liquid stools or >300 gm of loose or liquid stool
/24h), and/or vomiting during the inpatient period, in a participant with evidence of
infection. The secondary objectives are to determine the rate of infection in study
participants by; virus detection in stool by Norovirus GII.4 Challenge Stock-specific
qRT-PCR and anti- Norovirus GII.4 Challenge Stock serum IgG by ELISA (> /=4 fold rise from
baseline to Day 30), determine the quantity and duration of virus shedding in stool by
qRT-PCR, conduct Time-to-event analysis to estimate the median time to cessation of shedding
using Kaplan-Meier methods, determine the modified Vesikari score as a measure of
gastroenteritis severity, determine Norovirus GII.4 Challenge Stock-specific immunoglobulin
titers by ELISA before and after the challenge; Serum IgA and IgG, Serum Blockade IgG,
Salivary IgA, determine the effect of preexisting Norovirus GII.4 Challenge Stock-specific
Immunoglobulin in serum and saliva on the rate of infection, determine total and Norovirus
GII.4 Challenge Stock-specific IgA- and IgG-Secreting Cells in circulation by ELISpot assay.
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Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator)
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