Phase I Norovirus Challenge Model

Completed · Phase 1

Conditions studied: Gastroenteritis Norovirus

In brief

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.

Key facts

Study ID

NCT04174560

Run by

National Institute of Allergy and Infectious Diseases (NIAID)

People needed

48

Starts

2022-03-28

Expected to finish

2024-01-08

Last updated by the study team

2025-03-06

Who can join

Age: 18 and older, up to 49. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• Subject able to provide informed consent.
• Male or non-pregnant females between the ages of 18 and 49 years, inclusive.
• Women of childbearing potential must be using an acceptable method of birth control for at least 30 days prior to enrollment through day 45 after receipt of challenge virus.
• A woman is considered of childbearing potential unless post-menopausal (absence of menses for > / = 1 year) or surgically sterilized (tubal ligation, bilateral oophorectomy or hysterectomy).
• Acceptable contraception methods for women include but are not limited to: sexual abstinence from intercourse with men, monogamous relationship with vasectomized partner who has been vasectomized for 6 months or more prior to the subject enrolling in the study, barrier methods such as condoms or diaphragms with spermicide or foam, effective devices (intrauterine devices (IUD's), NuvaRing (R)) or licensed hormonal products such as implants, injectables or oral contraceptives.
• For women of childbearing potential, must have a negative serum or urine pregnancy test at screening.
• Are in good general health*.
• As determined by medical history and physical examination to evaluate acute or currently ongoing chronic medical diagnoses or conditions, defined as those that have been present for at least 90 days, which would affect the assessment of the safety of subjects. Chronic medical diagnoses or conditions should be stable for the last 60 days (no hospitalizations, Emergency Room (ER), or urgent care for condition and no adverse symptoms that need medical intervention such as medication change/supplemental oxygen). This includes no change in chronic prescription medication, dose, or frequency as a result of deterioration of the chronic medical diagnosis or condition in the 60 days prior to enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or that is done for financial reasons, as long as in the same class of medication, will not be considered a deviation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the site principal investigator or appropriate sub-investigator, will not be considered a deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site principal investigator or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening of medical diagnosis or condition. Similarly, medication changes subsequent to enrollment and study vaccination are acceptable provided there was no deterioration in the subject's chronic medical condition that necessitated a medication change, and there is no additional risk to the subject or interference with the evaluation of responses to study vaccination.
• Demonstrate knowledge and comprehension of the study by scoring > / = 70% on a quiz (test of understanding) of the study protocol and policies.
• Willing and able to participate in all study visits, including an inpatient stay of at least 96 hours.

You may not qualify if…

• Have household contact with or have daily contact with children less than 2 years of age or persons older than 70 years of age.
• 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).
• 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.
• Are positive for COVID-19 by an antigen test at the time of admission to the challenge unit.
• Are food service workers expected to prepare/handle food in the 8 weeks after challenge.
• Plan to be living in a confined communal environment (e.g. ship, camp, or dormitory) within 8 weeks after receiving the challenge strain.
• 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.
• Are breastfeeding or plan to breastfeed at any given time throughout the study.
• Have a history of acute gastroenteritis in the 4 weeks prior to challenge or any history of chronic or recurrent diarrhea or vomiting.
• 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.
• Have significant acute illness or an oral temperature > /= 100.4 degrees Fahrenheit within seven days prior to challenge.
• 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.
• 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.
• Diastolic blood pressure less than 50 mm Hg or greater than 90 mm Hg on two separate measurements (screening and baseline, prior to challenge).
• 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.
• Have an autoimmune, inflammatory, vasculitic or rheumatic disease, including but not limited to systemic lupus erythematosus, polymyalgia rheumatica, rheumatoid arthritis or scleroderma.
• 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.
• Have a seizure disorder.
• 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.

Where it is running

• Cincinnati Children's Hospital Medical Center Vaccine Research Center — Cincinnati, Ohio, United States

Full record on ClinicalTrials.gov

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