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Phase I Study to Determine the Optimal Human Challenge Dose for a Norovirus GII.4 Challenge Stock (CIN-1) | Clinical Trials | Clareo Health

WITHDRAWNPHASE1

Phase I Study to Determine the Optimal Human Challenge Dose for a Norovirus GII.4 Challenge Stock (CIN-1)

NCT02337842•National Institute of Allergy and Infectious Diseases (NIAID)

View on ClinicalTrials.gov

Summary

This is phase I, double blind, placebo-controlled safety and infectivity study of experimental human Norovirus genogroup GII.4 administered to healthy adults 18-49 years of age. Subjects susceptible to the human norovirus GII.4 challenge strain. The challenge study will be conducted in 2-3 cohorts of approximately 20 subjects each.Subjects will remain in the inpatient facility for at least four days following challenge and assessed daily for clinical and virologic evidence of norovirus infection. The primary objectives are to evaluate the safety and reactogenicity of the norovirus GII.4 (CIN-1; 031693) challenge stock and to determine a safe and optimal challenge dose of Norovirus GII.4 Challenge Stock norovirus to achieve illness in \> /=50% of subjects. Illness is defined as: diarrhea (\>3 loose or liquid stools or \>300 gm of loose or liquid stool /24h), and/or vomiting during the inpatient period, in a participant with evidence of infection.

Detailed Description

This is phase I, double blind, placebo-controlled safety and infectivity study of experimental human Norovirus genogroup GII.4 administered to healthy adults 18-49 years of age. The unblinded pharmacist will assign treatments. Subjects will be admitted to an inpatient nursing unit, challenged with live GII.4 Norovirus strain by oral administration, remain in the unit for at least 4 days following challenge and then followed for post-challenge safety and efficacy with multiple clinical assessments and collection of blood and stool specimens. Subjects susceptible to the human norovirus GII.4 challenge strain, CIN-1 (i.e. presence of a functional FUT-2 gene), regardless of ABO blood type, will be housed in the Cincinnati Center for Clinical Research (CCCR) inpatient facility and challenged orally with different doses of the virus. The challenge study will be conducted in 2-3 cohorts of approximately 20 subjects each, with the initial cohort receiving 103 RT-PCR units or placebo (9 "challenge" and 1 "placebo" per 10 subjects). Based on the illness rate of acute gastroenteritis (AGE) in the initial cohort, the second cohort will be enrolled to receive a challenge dose based on the results of the previous studies. Additional cohorts may be necessary. Illness is defined as infection accompanied by vomiting and/or diarrhea during the inpatient stay.Two to three additional subjects per cohort will serve as alternates in the event that any of the study subjects are unavailable or become ineligible at the time of the inpatient study.Subjects will remain in the inpatient facility for at least four days following challenge and assessed daily for clinical and virologic evidence of norovirus infection. Subjects will return to the investigational site for evaluation on Day 6 (6-8 days) and about 15 (14-16 days) and 30 days (28-35 days), and 45 (40-45 days), and (55-65) post challenge. The primary objectives are to evaluate the safety and reactogenicity of the norovirus GII.4 (CIN-1; 031693) challenge stock and to determine a safe and optimal challenge dose of Norovirus GII.4 Challenge Stock norovirus to achieve illness in \> /=50% of subjects. Illness is defined as: diarrhea (\>3 loose or liquid stools or \>300 gm of loose or liquid stool /24h), and/or vomiting during the inpatient period, in a participant with evidence of infection. The secondary objectives are to determine the rate of infection in study participants by; virus detection in stool by Norovirus GII.4 Challenge Stock-specific qRT-PCR and anti- Norovirus GII.4 Challenge Stock serum IgG by ELISA (\> /=4 fold rise from baseline to Day 30), determine the quantity and duration of virus shedding in stool by qRT-PCR, conduct Time-to-event analysis to estimate the median time to cessation of shedding using Kaplan-Meier methods, determine the modified Vesikari score as a measure of gastroenteritis severity, determine Norovirus GII.4 Challenge Stock-specific immunoglobulin titers by ELISA before and after the challenge; Serum IgA and IgG, Serum Blockade IgG, Salivary IgA, determine the effect of preexisting Norovirus GII.4 Challenge Stock-specific Immunoglobulin in serum and saliva on the rate of infection, determine total and Norovirus GII.4 Challenge Stock-specific IgA- and IgG-Secreting Cells in circulation by ELISpot assay.

Eligibility

Age

18 - 49 years

Sex

ALL

Healthy Volunteers

Yes

Inclusion Criteria

•Subject able to provide written informed consent.
•Male or non-pregnant females between the ages of 18 and 49 years, inclusive.
•Women of childbearing potential must be practicing abstinence or using an acceptable method of birth control for at least 30 days prior to enrollment through day 45 after receipt of the challenge virus. Male subjects must agree not to father a child prior to day 45 after receipt of the 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 (IUDs, NuvaRing®) 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 and negative urine or serum pregnancy test within 24 hours prior to challenge.
•Are in good general health, as determined by the study investigator within 60 days of challenge.
•Demonstrate knowledge and comprehension of the study by scoring \>/=70 procent on a quiz of the study protocol and policies.
•Willing and able to participate in all study visits, including an inpatient stay of at least 96 hours.
•Demonstrated to be secretor positive for HBGA binding.

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 occupational or social contact 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 patient contact in the 8 weeks after challenge.
•Are food service workers expected to prepare/handle food in the 8 weeks after challenge.
•Plan to be living in a confined 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 gastroenteritis in the 4 weeks prior to challenge or any history of chronic or recurrent diarrhea or vomiting.
•Have a history of malabsorption or maldigestion disorder (e.g. celiac sprue), major gastrointestinal (GI) surgery, irritable bowel syndrome or any other chronic GI disorders that would interfere with the study, including chronic constipation or increased stool frequency.
•Have moderate or severe illness and/or an oral temperature \>/=100.4 degre Fahrenheit and/or diarrhea or vomiting within seven days prior to challenge.
+30 more criteria

Locations (1)

Cincinnati Children's Hospital Medical Center - Infectious Diseases

Cincinnati, Ohio, United States

Key Dates

Start Date

September 1, 2015

Primary Completion Date

January 1, 2016

Completion Date

January 1, 2016

Last Updated

June 3, 2016

Conditions

Gastroenteritis Norovirus

Interventions

Norovirus GII.4 Challenge Pool CIN-1

BIOLOGICAL

Placebo

OTHER

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: June 3, 2016Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

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