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Phase 1 N=48 Triple-blind Basic Science

Phase I Norovirus Challenge Model

Gastroenteritis Norovirus

Enrolled (actual)
48
Serious AEs
0.0%
Results posted
Nov 2024
Primary outcome: Primary: The Occurrence of Norovirus-associated Illness in Secretor Positive Participants Through Day 4 After Challenge. — 3; 2; 7; 0 Participants

Study Design & Population

Study type
Interventional
Phase
Phase 1
Interventions
Norovirus GII.4 Challenge Pool (Biological)
Age
Adult · 18+ yrs
Sex
All
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Primary completion
Jul 2023

Outcome Measures

OutcomeResultp-value
PRIMARY
The Occurrence of Norovirus-associated Illness in Secretor Positive Participants Through Day 4 After Challenge.
3; 2; 7; 0
SECONDARY
The Number of Participants With Solicited Adverse Events Through Day 10
10; 10; 15; 3
SECONDARY
The Number of Participants With Unsolicited Serious Adverse Events Reported Through Day 180.
0; 0; 0; 0
SECONDARY
The Number of Participants With Unsolicited Grade 3 Adverse Events From Challenge to Day 30
0; 0; 2; 0
SECONDARY
The Number of Participants With Infection Through Day 30
4; 4; 9; 0; 3; 4
SECONDARY
Peak Genome Equivalent Copies/mL of Virus in Stool as Measured by qRT-PCR After Challenge Through Day 60
230475280.31; 43569331.414; 176337339.33
SECONDARY
Duration (Number of Days) of Viral Secretion as Measured by qRT-PCR After Challenge Through Day 60
5; 9.8; 3.9
SECONDARY
Modified Vesikari Score Through Day 4
2.5; 3.1; 3.8; 2.7
SECONDARY
Duration (Hours) of Vomiting and/or Diarrhea Through Day 5
11.02; 7.015; 17.264; 11.655; 2.5; 6.62

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.

Eligibility Criteria

Inclusion Criteria

  • 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.

Exclusion Criteria

  • 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 /= 100.4 degrees Fahrenheit within seven days prior to challenge.

  • Have a heart rate 100 bpm*.

*If heart rate is 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 measur
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04174560). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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