Gastroenteritis NorovirusPhase 1NCT02337842
Phase I Study to Determine the Optimal Human Challenge Dose for a Norovirus GII.4 Challenge Stock (CIN-1)
A Phase 1 study testing Norovirus GII.4 Challenge Pool CIN-1 in people with Gastroenteritis Norovirus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 49 yearsHealthy volunteers can take part
- Conditions the study is for
- Gastroenteritis Norovirus
- What is being tested?
- Norovirus GII.4 Challenge Pool CIN-1
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2015to Jan 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 49 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects must meet all of the following 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.
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- 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.
Who cannot join
- Subjects who meet any of the following exclusion criteria will be excluded from study participation:
- 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.
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- 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.
- Have a pulse rate less than 55 bpm or greater than 100 bpm. If heart rate is <55 beats per minute and the investigator determines that this is not clinically significant (e.g., athletes) and heart rate increases > 55 beats per minute on moderate exercise (two flights of stairs), subject will not be excluded.
- Have a systolic blood pressure less than 90 mm Hg or greater than 140 mm Hg on two separate measurements (screening and pre-challenge).
- Have a diastolic blood pressure less than 50 mm Hg or greater than 90 mmHg on two separate measurements (screening and pre-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 rheumatic, rheumatoid arthritis or scleroderma.
- Have HIV, Hepatitis B, Hepatitis C infection or untreated latent syphilis.
- Have a seizure disorder.
- Have an active malignancy or history of malignancy (excluding nonmelanotic skin cancer in remission without treatment for more than 5 years) or current use of immunosuppressive or cytotoxic therapy.
- Have positive fecal culture for E. coli O157:H7, Salmonella, Campylobacter, Yersinia, or Shigella, evidence of norovirus in the stool by RT-qPCR or pathogenic ova and parasites detected on microscopic examination at screening.
- Have abnormal screening laboratory test results per laboratory reported normal values and Section 18 Appendix B for white blood cells (WBCs), hemoglobin (Hgb), platelets, absolute neutrophil count (ANC), bilirubin, potassium, sodium, Hemoglobin A1-c (HgbA1-c) and urine protein.
- Serum creatinine greater than 1.1 x ULN
- Alanine aminotransferase (ALT), greater than 1.1 x ULN.
- 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.
- Have abnormal findings on screening electrocardiogram deemed clinically significant by study physician.
- Have ongoing drug abuse/dependence (including alcohol), or a history of these issues within 5 years of enrollment.
- Have a positive urine test for opiates.
- 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.
- Are unwilling to comply with study procedures including abstaining from smoking for the duration of the inpatient portion of the study.
- Have participated in a previous NoV challenge study or NoV vaccine study.
- Have received experimental products within 30 days before study entry or plan to receive experimental products at any time during the study.
- 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.
- Plan to donate blood during the course of the study.
- 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.
- Have received an inactivated vaccine within 14 days before study entry or plan to receive an inactivated vaccine prior to Day 14 of the study.
- Have received parenteral immunoglobulin or blood products within 3 months of the study start, or plan to receive parenteral immunoglobulin or blood products within 3 months after receiving the study agent.
- Use of antibiotics within 7 days prior to entry into the inpatient facility.
- Use of any H2 receptor antagonists (e.g., Tagamet, Zantac, and Pepcid), proton pump inhibitors (e.g., Prilosec, OTC, Protonix, and Prevacid), or prescription acid suppression medication or over-the-counter (OTC) antacids in the 72 hours prior to NoV challenge.
- Use of prescription and OTC medications containing acetaminophen, aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs within 48 hours prior to NoV challenge.
- Regular use of laxatives or anti-motility agents.
- Have a history of allergy to sodium bicarbonate.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center - Infectious Diseases
Cincinnati, Ohio, 45229-3026
About this study
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.
Read the 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.
- Conditions
- Gastroenteritis Norovirus
- Being tested
- Norovirus GII.4 Challenge Pool CIN-1, Placebo
- Keywords
- NoV, CIN-1, GII4. Norovirus, challenge, FUT-2 gene, HBGA-blocking Ab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Norovirus GII.4 Challenge Pool CIN-1Biological
Norovirus Challenge GII.4 Strain 031693. Cohort 1: receive single oral dose of GII.4 CIN-1 at 10^3 RT-PCR units. Cohort 2: single oral dose of GII.4 CIN-1 either at 10^2 or 5x10^3 RT-PCR units. Cohort 3: single oral dose of GII.4 CIN-1 at either 10^4, 10^3, 5x10^2 or 5x10^1 RT-PCR units. Cohort 4: single oral dose of GII.4 CIN-1 at either 5x10^4 or 5x10^3 or 10^3 or 10^2 or 10^4 or 5x10^2 or 5x10^1RT-PCR units.
PlaceboOther
Placebo: 80 ml of sterile water for oral administration
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | N= 9 subjects will receive single oral dose of GII.4 CIN-1 at 10^3 RT-PCR units and N=1 single oral dose Placebo. Receives: Biological: Norovirus GII.4 Challenge Pool CIN-1; Other: Placebo |
| Cohort 2 | Experimental | N=9 subjects will receive single oral dose of GII.4 CIN-1 either at 10^2 or 5x10^3 RT-PCR units and N=1 single oral dose of Placebo. Receives: Biological: Norovirus GII.4 Challenge Pool CIN-1; Other: Placebo |
| Cohort 4 | Experimental | N=36 subjects will receive single oral dose of GII.4 CIN-1 at either 5x10^4 or 5x10^3 or 10^3 or 10^2 or 10^4 or 5x10^2 or 5x10^1RT-PCR units , N=4 subjects receive a single oral dose of Placebo Receives: Biological: Norovirus GII.4 Challenge Pool CIN-1; Other: Placebo |
| Cohort 3 | Experimental | N=18 subjects will receive single oral dose of GII.4 CIN-1 at either 10^4, 10^3, 5x10^2 or 5x10^1 RT-PCR units and N=2 single oral dose of Placebo Receives: Biological: Norovirus GII.4 Challenge Pool CIN-1; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects experiencing any mild, moderate or severe reactogenicity outcomes.
Measured: Day 1 to Day 180
Proportion of subjects with Norovirus-GII.4 Challenge Stock (CIN-1; 031693) associated illness following norovirus GII.4 challenge
Measured: Day 1 to Day 5
Number of serious adverse events related to virus challenge reported at any point during the study
Measured: Day 1 to Day 180
Number of subjects experiencing Grade 3 adverse events after virus challenge throughout the study to day 30
Measured: Day 1 to Day 30
Determine Infectious Dose50 based on infection rate after challenge with various doses.
Measured: Day 1 to Day 180
Secondary outcomes (11)
Infection rate within each dose, defined as proportion of subjects excreting challenge virus in stool 24 hours after challenge
Measured: 24 hours after challenge
Proportion of subjects with norovirus specific IgG-ASC / 10^6 PBMC (freshly isolated PBMCs)
Measured: Day 1 to Day 45
Clinical Severity Score of vomiting and/or diarrhea related to the challenge strain using the Modified Vesikari Scale
Measured: Day 1 to Day 5
95% confidence intervals of vomiting and/or diarrhea related to the challenge strain
Measured: Day 1 to Day 5
Mean duration (hours) of vomiting and/or diarrhea related to the challenge strain
Measured: Day 1 to Day 5
At any time after challenge Proportion of subjects with >/= 4 fold rise from the baseline in virus-specific antibody titers in serum(IgA, IgG Blockade), or salivary IgA
Measured: Day 1 to Day 45
Infection rate within each dose defined as proportion of subjects showing a > /=4 fold rise in virus specific serum IgG from baseline to Day 30
Measured: Day 1 to Day 30
Proportion of subjects with norovirus specific IgA- ASC / 10^6 PBMC (freshly isolated PBMCs)
Measured: Day 1 to Day 45
Correlation of challenge outcome (infection) and preexisting serum immunoglobulins.
Measured: Day 1 to Day 45
Time-to-cessation of virus shedding in stool in hours for each challenge dose.
Measured: Day 1 to Day 60
Magnitude and duration of virus shedding in stool reported as qRT-PCR units for each challenge dose
Measured: Day 1 to Day 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2015 (estimated)
- Study startSep 2015
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastroenteritis NorovirusStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02337842
- Sponsor's protocol ID
- 12-0033
- Other IDs
- HHSN272200800006C
- Status last verified
- Aug 2015
- First submitted
- 8 Jan 2015
- Last updated
- 3 Jun 2016
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study to Determine the Optimal Human Challenge Dose for a Norovirus GII.4 Challenge Stock (CIN-1)
- ClinicalTrials.gov ID
- NCT02337842
- Acronym / sponsor ID
- 12-0033
- Conditions
- Gastroenteritis Norovirus
- Keywords
- NoV, CIN-1, GII4. Norovirus, challenge, FUT-2 gene, HBGA-blocking Ab
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Sep 2015
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 14 Jan 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: Norovirus GII.4 Challenge Pool CIN-1, Other: PlaceboN= 9 subjects will receive single oral dose of GII.4 CIN-1 at 10^3 RT-PCR units and N=1 single oral dose Placebo. |
| Cohort 2 | Experimental | Biological: Norovirus GII.4 Challenge Pool CIN-1, Other: PlaceboN=9 subjects will receive single oral dose of GII.4 CIN-1 either at 10^2 or 5x10^3 RT-PCR units and N=1 single oral dose of Placebo. |
| Cohort 4 | Experimental | Biological: Norovirus GII.4 Challenge Pool CIN-1, Other: PlaceboN=36 subjects will receive single oral dose of GII.4 CIN-1 at either 5x10^4 or 5x10^3 or 10^3 or 10^2 or 10^4 or 5x10^2 or 5x10^1RT-PCR units , N=4 subjects receive a single oral dose of Placebo |
| Cohort 3 | Experimental | Biological: Norovirus GII.4 Challenge Pool CIN-1, Other: PlaceboN=18 subjects will receive single oral dose of GII.4 CIN-1 at either 10^4, 10^3, 5x10^2 or 5x10^1 RT-PCR units and N=2 single oral dose of Placebo |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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.
- 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.
Key exclusion criteria (41 listed)
- Subjects who meet any of the following exclusion criteria will be excluded from study participation:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Norovirus GII.4 Challenge Pool CIN-1Norovirus Challenge GII.4 Strain 031693. Cohort 1: receive single oral dose of GII.4 CIN-1 at 10^3 RT-PCR units. Cohort 2: single oral dose of GII.4 CIN-1 either at 10^2 or 5x10^3 RT-PCR units. Cohort 3: single oral dose of GII.4 CIN-1 at either 10^4, 10^3, 5x10^2 or 5x10^1 RT-PCR units. Cohort 4: single oral dose of GII.4 CIN-1 at either 5x10^4 or 5x10^3 or 10^3 or 10^2 or 10^4 or 5x10^2 or 5x10^1RT-PCR units. | Biological | Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
| PlaceboPlacebo: 80 ml of sterile water for oral administration | Other | Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
Primary outcome
Number of subjects experiencing any mild, moderate or severe reactogenicity outcomes.
Time frame: Day 1 to Day 180
Proportion of subjects with Norovirus-GII.4 Challenge Stock (CIN-1; 031693) associated illness following norovirus GII.4 challenge
Time frame: Day 1 to Day 5
Number of serious adverse events related to virus challenge reported at any point during the study
Time frame: Day 1 to Day 180
Number of subjects experiencing Grade 3 adverse events after virus challenge throughout the study to day 30
Time frame: Day 1 to Day 30
Determine Infectious Dose50 based on infection rate after challenge with various doses.
Time frame: Day 1 to Day 180
11 secondary outcomes
Infection rate within each dose, defined as proportion of subjects excreting challenge virus in stool 24 hours after challenge
Time frame: 24 hours after challenge
Proportion of subjects with norovirus specific IgG-ASC / 10^6 PBMC (freshly isolated PBMCs)
Time frame: Day 1 to Day 45
Clinical Severity Score of vomiting and/or diarrhea related to the challenge strain using the Modified Vesikari Scale
Time frame: Day 1 to Day 5
95% confidence intervals of vomiting and/or diarrhea related to the challenge strain
Time frame: Day 1 to Day 5
Mean duration (hours) of vomiting and/or diarrhea related to the challenge strain
Time frame: Day 1 to Day 5
At any time after challenge Proportion of subjects with >/= 4 fold rise from the baseline in virus-specific antibody titers in serum(IgA, IgG Blockade), or salivary IgA
Time frame: Day 1 to Day 45
Infection rate within each dose defined as proportion of subjects showing a > /=4 fold rise in virus specific serum IgG from baseline to Day 30
Time frame: Day 1 to Day 30
Proportion of subjects with norovirus specific IgA- ASC / 10^6 PBMC (freshly isolated PBMCs)
Time frame: Day 1 to Day 45
Correlation of challenge outcome (infection) and preexisting serum immunoglobulins.
Time frame: Day 1 to Day 45
Time-to-cessation of virus shedding in stool in hours for each challenge dose.
Time frame: Day 1 to Day 60
Magnitude and duration of virus shedding in stool reported as qRT-PCR units for each challenge dose
Time frame: Day 1 to Day 60
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Norovirus GII.4 Challenge Pool CIN-1 in people with Gastroenteritis Norovirus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 3 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of subjects experiencing any mild, moderate or severe reactogenicity outcomes. (time frame: Day 1 to Day 180). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2016.