Phase I Norovirus Challenge Model

NCT04174560 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 17-0102
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Gastroenteritis Norovirus

Keywords

Healthy Adults; Norovirus GII.4 CIN-3; Optimal Human Challenge Dose

Outcome Measures

Primary Outcomes (1)

• The Occurrence of Norovirus-associated Illness in Secretor Positive Participants Through Day 4 After Challenge.

  Illness is defined as norovirus infection, determined by a positive 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, and/or c) any episode of vomiting.

  Day 1 through Day 4

Secondary Outcomes (8)

• The Number of Participants With Solicited Adverse Events Through Day 10

  Day 1 through Day 10

• The Number of Participants With Unsolicited Serious Adverse Events Reported Through Day 180.

  Day 1 through Day 180

• The Number of Participants With Unsolicited Grade 3 Adverse Events From Challenge to Day 30

  Day 1 through Day 30

• The Number of Participants With Infection Through Day 30

  Day 1 through Day 30

• Peak Genome Equivalent Copies/mL of Virus in Stool as Measured by qRT-PCR After Challenge Through Day 60

  Day 1 through Day 60

Study Arms (3)

Cohort 1

EXPERIMENTAL

Single dose (3.5x10\^3 copies) of norovirus GII.4 CIN-3 Batch No.: 01-16C3 inoculum (with 60 mL of a 2% sodium bicarbonate before and after inoculum administration) will be given orally to subjects with functional FUT-2 gene (secretor positive), n=15, and single dose (3.5x10\^3 copies) of norovirus GII.4 CIN-3 Batch No.: 01-16C3 inoculum (with 60 mL of a 2% sodium bicarbonate before and after inoculum administration) will be given to subjects with a lack a non-functional FUT-2 gene (non-secretor), n=1, on Day 1

Biological: Norovirus GII.4 Challenge Pool

Cohort 2

EXPERIMENTAL

Single dose (3.5x10\^4 copies) of norovirus GII.4 CIN-3 Batch No.: 01-16C3 inoculum (with 60 mL of a 2% sodium bicarbonate before and after inoculum administration) will be given orally to subjects with functional FUT-2 gene (secretor positive), n=15, and single dose (3.5x10\^4 copies) of norovirus GII.4 CIN-3 Batch No.: 01-16C3 inoculum (with 60 mL of a 2% sodium bicarbonate before and after inoculum administration) will be given to subjects with a lack a non-functional FUT-2 gene (non-secretor), n=1, on Day 1

Biological: Norovirus GII.4 Challenge Pool

Cohort 3

EXPERIMENTAL

Single dose (3.5x10\^5 copies) of norovirus GII.4 CIN-3 Batch No.: 01-16C3 inoculum (with 60 mL of a 2% sodium bicarbonate before and after inoculum administration) will be given orally to subjects with functional FUT-2 gene (secretor positive), n=15, and single dose (3.5x10\^5 copies) of norovirus GII.4 CIN-3 Batch No.: 01-16C3 inoculum (with 60 mL of a 2% sodium bicarbonate before and after inoculum administration) will be given to subjects with a lack a non-functional FUT-2 gene (non-secretor), n=1, on Day 1

Biological: Norovirus GII.4 Challenge Pool

Interventions

Norovirus GII.4 Challenge Pool BIOLOGICAL

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.

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

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\*.
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center Vaccine Research Center

Cincinnati, Ohio, 45229-3039, United States

Location

Results Point of Contact

• Title: Robert Frenck, Jr., MD
• Organization: Cincinnati Children's Hospital

Robert.Frenck@cchmc.org

513-636-4463

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2019
• First Posted: November 22, 2019
• Study Start: March 28, 2022
• Primary Completion: July 13, 2023
• Study Completion: January 8, 2024
• Last Updated: March 6, 2025
• Results First Posted: November 19, 2024

Record last verified: 2024-01-03

Locations

US (1)