NCT04174560

Phase I Norovirus Challenge Model

Phase I Study to Determine the Optimal Human Challenge Dose for Norovirus GII.4 CIN-3 Batch No.: 01-16C3

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (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 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.

Conditions

• Gastroenteritis Norovirus

Interventions

Type	Name	Description
BIOLOGICAL	Norovirus GII.4 Challenge Pool	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.

Timeline

• Start date: 2022-03-28
• Primary completion: 2023-07-13
• Completion: 2024-01-08
• First posted: 2019-11-22
• Last updated: 2025-03-06
• Results posted: 2024-11-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study