Phase I Norovirus Challenge Model

Exclusion Criteria

• •1. Have household contact with or have daily contact with children less than 2 years of age or persons older than 70 years of age.
• •2. Have expected extended social contact (\> 2 hours/day) with immunocompromised individuals in the 8 weeks after challenge\*.
• •\*Including persons with HIV infection or active cancer, children \<2 years of age, pregnant women or persons who are immunosuppressed (e.g. history of stem cell or organ transplantation) and/or provide any child day care services (in-home or non-residential facility).
• •3. Are healthcare workers with direct patient contact or any child day care services (in-home or non-residential facility) in the 8 weeks after challenge.
• •4. Are positive for COVID-19 by an antigen test at the time of admission to the challenge unit.
• •5. Are food service workers expected to prepare/handle food in the 8 weeks after challenge.
• •6. Plan to be living in a confined communal environment (e.g. ship, camp, or dormitory) within 8 weeks after receiving the challenge strain.
• •7. For females, are pregnant or plan to become pregnant at any time between the Screening Visit through 45 days after receipt of the challenge virus.
• •8. Are breastfeeding or plan to breastfeed at any given time throughout the study.
• •9. Have a history of acute gastroenteritis in the 4 weeks prior to challenge or any history of chronic or recurrent diarrhea or vomiting.
• •10. History of significant GI condition. \*
• •\*Including: malabsorption, major GI surgery, current \*eating disorder, irritable bowel syndrome, or any GI disorder (deemed clinically significant by study physician) making it unsafe to participate.
• •11. Have significant acute illness or an oral temperature \> /= 100.4 degrees Fahrenheit within seven days prior to challenge.
• •12. Have a heart rate \<45 beats per minute (bpm) or \>100 bpm\*.
• •\*If heart rate is \<45 beats per minute and the investigator determines that this is not clinically significant (e.g., athletes) and heart rate increases \> 45 beats per minute on moderate exercise (two flights of stairs), subject will not be excluded. If a subject has significant abnormalities in their heart rate, they will be informed of the values and advised to seek care from their physician.
• •13. Systolic blood pressure less than 90 mm Hg or greater than 150 mm Hg on two separate measurements (screening and baseline prior to challenge)\*.
• •\*If a subject has significant abnormalities in their blood pressure, they will be informed of the values and advised to seek care from their physician.
• •14. Diastolic blood pressure less than 50 mm Hg or greater than 90 mm Hg on two separate measurements (screening and baseline, prior to challenge).
• •15. Have long-term use (\> / = 2 weeks) of high-dose oral (\> / = 20 mg per day prednisone or equivalent) or parenteral glucocorticoids, or high-dose inhaled steroids for greater than 7 days in the last 6 months.
• •16. Have an autoimmune, inflammatory, vasculitic or rheumatic disease, including but not limited to systemic lupus erythematosus, polymyalgia rheumatica, rheumatoid arthritis or scleroderma.
• •17. Have HIV, Hepatitis B, or Hepatitis C\*.
• •\*Subjects will be tested for HIV, Hepatitis B surface antigen, and antibody to Hepatitis C at screening only. Any subjects having HIV, Hepatitis B, Hepatitis C infection will not be enrolled into the study.
• •18. Have a seizure disorder.
• •19. Have an active malignancy or history of malignancy\* or current use of immunosuppressive or cytotoxic therapy.
• •\*Excluding nonmelanotic skin cancer in remission without treatment for more than 5 years.
• •20. Have abnormal screening laboratory test results per laboratory reported normal values\*.
• •\*For white blood cells (WBCs), hemoglobin (Hgb), platelets, absolute neutrophil count (ANC), total bilirubin, potassium, sodium, and urine protein.
• •21. Serum creatinine greater than a Grade 1 adverse event on enrollment.
• •22. Alanine aminotransferase (ALT), greater than Grade 1 adverse event on enrollment.
• •23. Have a chronic condition that the study physician feels would pose a threat to participating subjects\*.
• •\*Including, but not limited to solid organ or stem cell transplantation, diabetes, clinically significant history of immunosuppressive illness, gall bladder disease, heart disease, lung disease, pancreatic disease, renal disease or neurological disease.
• •24. Have ongoing drug abuse/dependence (including alcohol), or a history of these issues within 5 years of enrollment.
• •25. Have a positive urine test for opiates.
• •26. Have any medical, psychiatric, occupational, or behavioral problems that make it unlikely for the subject to comply with the protocol as determined by the investigator.
• •27. Are unwilling to comply with study procedures including abstaining from smoking for the duration of the inpatient portion of the study.
• •28. Have participated in a previous norovirus (NoV) challenge study or NoV vaccine study.
• •29. Have received experimental products within 30 days before study entry or plan to receive experimental products at any time during the study.
• •30. Plans to enroll in another clinical trial that could interfere with safety assessment of the investigational product at any time during the study period\*.
• •\*Including study interventions such as drugs, biologics or devices.
• •31. Plan to donate blood during the course of the study.
• •32. Have received a live vaccine within 30 days before study entry or plan to receive a live vaccine prior to Day 30 of the study.
• •33. Have received, or plan to receive, an inactivated vaccine within 14 days of challenge to 14 days after challenge.
• •34. Received parenteral immunoglobulin or blood products within 3 months of challenge, or plan to receive parenteral immunoglobulin/blood products within 3 months after challenge.
• •35. Use of antibiotics within 7 days prior to entry into the inpatient facility.
• •36. Use of prescription and OTC medications containing acetaminophen, aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs within 48 hours prior to NoV challenge.
• •37. Regular use of laxatives or anti-motility agents.
• •38. Have a history of allergy to sodium bicarbonate.
• •39. Have had a recent norovirus infection or have ever had a norovirus vaccine.