Gastroenteritis NorovirusPhase 1NCT02473224
Optimal Human Dose for GII.2 Norovirus (Snow Mountain) Challenge Studies
A Phase 1 study testing Norovirus GII.2 Challenge 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 a phase I, randomized, double blind, as well as partially blinded (for Cohort 4), placebo-controlled safety, illness, and infection study of a new experimental human challenge stock of the Norovirus genogroup II, genotype 2 (GII.2) isolate designated Snow Mountain virus (SMV). 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.2 Challenge
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Oct 2015to 27 Nov 2018
- 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
- 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 pregnancy test within 24 hours prior to challenge
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- 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 percent 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 H type I secretor positive for HBGA binding by assay of saliva (this applies to all cohorts except the SN cohort, which will include secretor negative subjects only)
Who cannot join
- Have household contact with or have daily contact with children under 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). Individuals who provide any child day care services (in-home or non-residential facility) are also excluded
- 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
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- 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 degrees F and/or diarrhea or vomiting within seven days prior to challenge
- Have a pulse rate less than 55 beats per minute (bpm) or greater than 100 bpm. If heart rate is <55 bpm and the investigator determines that this is not clinically significant (e.g., athletes) and heart rate increases > 55 bpm on moderate exercise (two flights of stairs), subject will not be excluded
- Have a systolic blood pressure less than 90 mmHg or greater than 140 mmHg on two separate measurements (screening and pre-challenge)
- Have a diastolic blood pressure less than 50 mmHg 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, 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 for white blood cells (WBCs), hemoglobin (Hgb), platelets, absolute neutrophil count (ANC), elevated total bilirubin, potassium, sodium and hemoglobin A1c (HbA1c) and urine protein
- Have a serum creatinine greater than 1.1 x ULN
- Have an ALT (SGPT) 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 24. Have abnormal findings on screening electrocardiogram deemed clinically significant by study physician
- 25. Have ongoing drug abuse/dependence (including alcohol), or a history of these issues within 5 years of enrollment 26. Have a positive urine test for opiates 27. 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 28. Are unwilling to comply with study procedures including abstaining from smoking for the duration of the inpatient portion of the study 29. Have participated in a previous NoV challenge study or NoV vaccine study 30. Have received experimental products within 30 days before study entry or plan to receive experimental products at any time during the study 31. 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 32. Plan to donate blood during the course of the study 33. 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 34. 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 35. 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 36. Use of antibiotics within 7 days prior to entry into the inpatient facility 37. Use of any H2 receptor antagonists (e.g., Tagamet, Zantac, and Pepcid), proton pump inhibitors (e.g., Prilosec, Protonix, and Prevacid), or prescription acid suppression medication or over-the-counter (OTC) antacids in the 72 hours prior to NoV challenge 38. Use of prescription and OTC medications containing acetaminophen, aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs within 48 hours prior to NoV challenge 39. Regular use of laxatives or anti-motility agents 40. Have a history of allergy to sodium bicarbonate 40. Have a history of allergy to sodium bicarbonate
Trial locations and contacts
1 site in 1 country.
United States1 site
Emory Vaccine Center - The Hope Clinic
Decatur, Georgia, 30030-1705
About this study
Official title: Phase I Study to Determine the Optimal Human Dose for GII.2 Norovirus (Snow Mountain) Challenge Studies
This is a phase I, randomized, double blind, as well as partially blinded (for Cohort 4), placebo-controlled safety, illness, and infection study of a new experimental human challenge stock of the Norovirus genogroup II, genotype 2 (GII.2) isolate designated Snow Mountain virus (SMV). The study duration is 24 - 36 months. The primary objectives are to: 1) evaluate the safety and reactogenicity of the GII.2 Snow Mountain norovirus challenge stock and 2) determine a safe and optimal challenge dose of GII.2 Snow Mountain norovirus to achieve illness in a high proportion (= / > 75%) of subjects.
Read the detailed description
This is a phase I, randomized, double blind, as well as partially blinded (for Cohort 4), placebo-controlled safety, illness, and infection study of a new experimental human challenge stock of the Norovirus genogroup II, genotype 2 (GII.2) isolate designated Snow Mountain virus (SMV), administered to healthy adults 18-49 years of age. Groups of 11 subjects each will be admitted to the inpatient hospital research unit, challenged with live SMV or placebo by oral administration, and remain in isolation in the unit for at least 4 days following challenge. The study duration is 24 - 36 months. Subjects will be followed post-challenge for safety, reactogenicity, and illness (primary objectives), and secondary or exploratory objectives including infection and immune responses. There will be multiple clinical assessments and collection of blood, emesis, saliva, and stool specimens. The primary objectives are to: 1) evaluate the safety and reactogenicity of the GII.2 Snow Mountain norovirus challenge stock and 2) determine a safe and optimal challenge dose of GII.2 Snow Mountain norovirus to achieve illness in a high proportion (= / > 75%) of subjects. The secondary objectives are to: 1) determine the rate of infection in study participants after norovirus GII.2 challenge, 2) determine the quantity and duration of virus shedding in stool by RT-qPCR, 3) estimate the median time to cessation of shedding, 4) determine the modified Vesikari score as a measure of gastroenteritis severity, 5) determine GII.2 Snow Mountain norovirus-specific Immunoglobulin titers by ELISA before and after the challenge, 6) determine the effect of pre-existing GII.2 Snow Mountain norovirus-specific immunoglobulin in serum and saliva on the rate of infection, 7) determine total and GII.2 Snow Mountain norovirus-specific IgA- and IgG-Secreting Cells in circulation by ELISpot assay, 8) once the optimal challenge dose is determined in secretor positive subjects: investigate the safety and illness rate using that dose of the GII.2 challenge stock in secretor negative subjects.
- Conditions
- Gastroenteritis Norovirus
- Being tested
- Norovirus GII.2 Challenge, Placebo
- Keywords
- challenge, GII.2, HID50, Norovirus, Snow Mountain filtrate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Norovirus GII.2 ChallengeBiological
GII.2 Snow Mountain Norovirus Filtrate. Cohort 1: 1.2x10^4 Genome Equivalent Copies (GEC) oral dose on Day 1. Cohort 2: either 1.2 x 10^2 GEC or 1.2 x10^6 GEC oral dose on Day 1, depending on the results of prior Cohort 1. Cohort 3: either 1GEC, 1.2 x 10^1 GEC, 1.2 x 10^2 GEC, 1.2 x 10^3 GEC, 1.2 x 10^5 GEC, or 1.2 x 10^6 GEC, or 1.2 GEC x 10^7 oral dose on Day 1, depending on the percentage of subjects with illness from Cohorts 1 and 2. Cohort 4: optimal dose of GEC as determined by the results of cohorts 1-3
PlaceboOther
Placebo: 80 ml of sterile water for oral administration
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 9 secretor-positive subjects will receive 1.2x10^4 Genome Equivalent Copies (GEC) oral dose on Day 1; and 2 secretor-positive subjects will receive the placebo, n=11 Receives: Biological: Norovirus GII.2 Challenge; Other: Placebo |
| Cohort 2 | Experimental | 9 secretor-positive subjects will receive either 1.2 x 10^2GEC, or 1.2 x10^6 GEC oral dose on Day 1, depending on the percentage of subjects with illness from Cohort 1; 2 secretor-positive subjects will receive the placebo, n=11 Receives: Biological: Norovirus GII.2 Challenge; Other: Placebo |
| Cohort 3 | Experimental | 9 secretor-positive subjects will receive either 1GEC, 1.2 x 10^1 GEC, 1.2 x 10^2 GEC, 1.2 x 10^3 GEC, 1.2 x 10^5 GEC, 1.2 x 10^6 GEC, or 1.2 x 10^7 oral dose on Day 1, depending on the percentage of subjects with illness from Cohorts 1 and 2; 2 secretor-positive subjects will receive the placebo, n=11 Receives: Biological: Norovirus GII.2 Challenge; Other: Placebo |
| Cohort 4 | Experimental | 8 secretor-negative and 3 secretor-positive subjects will receive 1.2 x 10^7 GEC oral dose on Day 1, n=11 Receives: Biological: Norovirus GII.2 Challenge; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Infectious Dose-50 based on infection rate after challenge with various doses
Measured: Day 2 to Day 5
Number of serious adverse events related to virus challenge
Measured: Day 1 to Day 180
Number of subjects experiencing any mild reactogenicity outcomes
Measured: Day 1 to Day 10
Number of subjects experiencing any moderate reactogenicity outcomes
Measured: Day 1 to Day 10
Number of subjects experiencing any severe reactogenicity outcomes
Measured: Day 1 to Day 10
Number of subjects experiencing Grade 3 adverse events
Measured: Day 1 to Day 30
Proportion of subjects with GII.2 Snow Mountain norovirus-associated illness following GII.2 challenge
Measured: Day 1 to Day 5
Secondary outcomes (18)
Duration of diarrhea related to the challenge strain
Measured: Day 1 to Day 5
Duration of virus shedding in PCR-positive stool for each challenge dose
Measured: Day -60 to Day 75
Duration of vomiting related to the challenge strain
Measured: Day 1 to Day 5
Levels of pre-existing serum blockage IgG prior to challenge
Measured: Inpatient Admission
Levels of pre-existing serum IgA prior to challenge
Measured: Inpatient Admission
Levels of pre-existing serum IgG prior to challenge
Measured: Inpatient Admission
Levels of pre-existing serum salivary IgA prior to challenge
Measured: Inpatient Admission
Magnitude of virus shedding in PCR-positive stools, reported as GEC/ml
Measured: Day -60 to Day 75
Proportion of subjects excreting challenge virus in stool
Measured: Day 1 to Day 30
Proportion of subjects showing a >/= 4 fold rise in virus-specific serum IgG
Measured: Day 1 to Day 30
Proportion of subjects with =/> 4 fold rise in virus-specific salivary IgA
Measured: Day 1 to Day 45
Proportion of subjects with =/> 4 fold rise in virus-specific serum blockage IgG
Measured: Day 1 to Day 45
Proportion of subjects with =/> 4 fold rise in virus-specific serum IgG
Measured: Day 1 to Day 45
Proportion of subjects with >/= 4 fold rise in virus-specific serum IgA
Measured: Day 1 to Day 45
Proportion of subjects with norovirus specific IgA-ASC/10^6 PBMC (freshly isolated PBMCs)
Measured: Day 1 to Day 45
Proportion of subjects with norovirus specific IgG-ASC/10^6 PBMC (freshly isolated PBMCs)
Measured: Day 1 to Day 45
Severity of diarrhea related to the challenge strain, determined using the Vesikari Score
Measured: Day 1 to Day 5
Severity of vomiting related to the challenge strain, determined using the Vesikari Score
Measured: Day 1 to Day 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2015 (estimated)
- Study start28 Oct 2015
- Primary completion27 Nov 2018
- Study completion27 Nov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02473224
- Sponsor's protocol ID
- 12-0034
- Status last verified
- 15 Jun 2018
- First submitted
- 4 Jun 2015
- Last updated
- 7 Dec 2018
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Rouphael N, Beck A, Kirby AE, Liu P, Natrajan MS, Lai L, Phadke V, Winston J, Raabe V, Collins MH, Girmay T, Alvarez A, Beydoun N, Karmali V, Altieri-Rivera J, Lindesmith LC, Anderson EJ, Wang Y, El-Khorazaty J, Petrie C, Baric RS, Baqar S, Moe CL, Mulligan MJ. Dose-Response of a Norovirus GII.2 Controlled Human Challenge Model Inoculum. J Infect Dis. 2022 Nov 11;226(10):1771-1780. doi: 10.1093/infdis/jiac045.
PubMed 35137154
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study to Determine the Optimal Human Dose for GII.2 Norovirus (Snow Mountain) Challenge Studies
- ClinicalTrials.gov ID
- NCT02473224
- Acronym / sponsor ID
- 12-0034
- Conditions
- Gastroenteritis Norovirus
- Keywords
- challenge, GII.2, HID50, Norovirus, Snow Mountain filtrate
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 28 Oct 2015 (actual)
- Primary completion
- 27 Nov 2018 (actual)
- Study completion
- 27 Nov 2018 (actual)
- First posted
- 16 Jun 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 a phase I, randomized, double blind, as well as partially blinded (for Cohort 4), placebo-controlled safety, illness, and infection study of a new experimental human challenge stock of the Norovirus genogroup II, genotype 2 (GII.2) isolate designated Snow Mountain virus (SMV). The study duration is 24 - 36 months. The primary objectives are to: 1) evaluate the safety and reactogenicity of the GII.2 Snow Mountain norovirus challenge stock and 2) determine a safe and optimal challenge dose of GII.2 Snow Mountain norovirus to achieve illness in a high proportion (= / > 75%) of subjects.
Detailed description
This is a phase I, randomized, double blind, as well as partially blinded (for Cohort 4), placebo-controlled safety, illness, and infection study of a new experimental human challenge stock of the Norovirus genogroup II, genotype 2 (GII.2) isolate designated Snow Mountain virus (SMV), administered to healthy adults 18-49 years of age. Groups of 11 subjects each will be admitted to the inpatient hospital research unit, challenged with live SMV or placebo by oral administration, and remain in isolation in the unit for at least 4 days following challenge. The study duration is 24 - 36 months. Subjects will be followed post-challenge for safety, reactogenicity, and illness (primary objectives), and secondary or exploratory objectives including infection and immune responses. There will be multiple clinical assessments and collection of blood, emesis, saliva, and stool specimens. The primary objectives are to: 1) evaluate the safety and reactogenicity of the GII.2 Snow Mountain norovirus challenge stock and 2) determine a safe and optimal challenge dose of GII.2 Snow Mountain norovirus to achieve illness in a high proportion (= / > 75%) of subjects. The secondary objectives are to: 1) determine the rate of infection in study participants after norovirus GII.2 challenge, 2) determine the quantity and duration of virus shedding in stool by RT-qPCR, 3) estimate the median time to cessation of shedding, 4) determine the modified Vesikari score as a measure of gastroenteritis severity, 5) determine GII.2 Snow Mountain norovirus-specific Immunoglobulin titers by ELISA before and after the challenge, 6) determine the effect of pre-existing GII.2 Snow Mountain norovirus-specific immunoglobulin in serum and saliva on the rate of infection, 7) determine total and GII.2 Snow Mountain norovirus-specific IgA- and IgG-Secreting Cells in circulation by ELISpot assay, 8) once the optimal challenge dose is determined in secretor positive subjects: investigate the safety and illness rate using that dose of the GII.2 challenge stock in secretor negative subjects.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: Norovirus GII.2 Challenge, Other: Placebo9 secretor-positive subjects will receive 1.2x10^4 Genome Equivalent Copies (GEC) oral dose on Day 1; and 2 secretor-positive subjects will receive the placebo, n=11 |
| Cohort 2 | Experimental | Biological: Norovirus GII.2 Challenge, Other: Placebo9 secretor-positive subjects will receive either 1.2 x 10^2GEC, or 1.2 x10^6 GEC oral dose on Day 1, depending on the percentage of subjects with illness from Cohort 1; 2 secretor-positive subjects will receive the placebo, n=11 |
| Cohort 3 | Experimental | Biological: Norovirus GII.2 Challenge, Other: Placebo9 secretor-positive subjects will receive either 1GEC, 1.2 x 10^1 GEC, 1.2 x 10^2 GEC, 1.2 x 10^3 GEC, 1.2 x 10^5 GEC, 1.2 x 10^6 GEC, or 1.2 x 10^7 oral dose on Day 1, depending on the percentage of subjects with illness from Cohorts 1 and 2; 2 secretor-positive subjects will receive the placebo, n=11 |
| Cohort 4 | Experimental | Biological: Norovirus GII.2 Challenge, Other: Placebo8 secretor-negative and 3 secretor-positive subjects will receive 1.2 x 10^7 GEC oral dose on Day 1, n=11 |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 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 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 (24 listed)
- Have household contact with or have daily contact with children under 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). Individuals who provide any child day care services (in-home or non-residential facility) are also excluded
- 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
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.2 ChallengeGII.2 Snow Mountain Norovirus Filtrate. Cohort 1: 1.2x10^4 Genome Equivalent Copies (GEC) oral dose on Day 1. Cohort 2: either 1.2 x 10^2 GEC or 1.2 x10^6 GEC oral dose on Day 1, depending on the results of prior Cohort 1. Cohort 3: either 1GEC, 1.2 x 10^1 GEC, 1.2 x 10^2 GEC, 1.2 x 10^3 GEC, 1.2 x 10^5 GEC, or 1.2 x 10^6 GEC, or 1.2 GEC x 10^7 oral dose on Day 1, depending on the percentage of subjects with illness from Cohorts 1 and 2. Cohort 4: optimal dose of GEC as determined by the results of cohorts 1-3 | 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
Infectious Dose-50 based on infection rate after challenge with various doses
Time frame: Day 2 to Day 5
Number of serious adverse events related to virus challenge
Time frame: Day 1 to Day 180
Number of subjects experiencing any mild reactogenicity outcomes
Time frame: Day 1 to Day 10
Number of subjects experiencing any moderate reactogenicity outcomes
Time frame: Day 1 to Day 10
Number of subjects experiencing any severe reactogenicity outcomes
Time frame: Day 1 to Day 10
Number of subjects experiencing Grade 3 adverse events
Time frame: Day 1 to Day 30
Proportion of subjects with GII.2 Snow Mountain norovirus-associated illness following GII.2 challenge
Time frame: Day 1 to Day 5
18 secondary outcomes
Duration of diarrhea related to the challenge strain
Time frame: Day 1 to Day 5
Duration of virus shedding in PCR-positive stool for each challenge dose
Time frame: Day -60 to Day 75
Duration of vomiting related to the challenge strain
Time frame: Day 1 to Day 5
Levels of pre-existing serum blockage IgG prior to challenge
Time frame: Inpatient Admission
Levels of pre-existing serum IgA prior to challenge
Time frame: Inpatient Admission
Levels of pre-existing serum IgG prior to challenge
Time frame: Inpatient Admission
Levels of pre-existing serum salivary IgA prior to challenge
Time frame: Inpatient Admission
Magnitude of virus shedding in PCR-positive stools, reported as GEC/ml
Time frame: Day -60 to Day 75
Proportion of subjects excreting challenge virus in stool
Time frame: Day 1 to Day 30
Proportion of subjects showing a >/= 4 fold rise in virus-specific serum IgG
Time frame: Day 1 to Day 30
Proportion of subjects with =/> 4 fold rise in virus-specific salivary IgA
Time frame: Day 1 to Day 45
Proportion of subjects with =/> 4 fold rise in virus-specific serum blockage IgG
Time frame: Day 1 to Day 45
Proportion of subjects with =/> 4 fold rise in virus-specific serum IgG
Time frame: Day 1 to Day 45
Proportion of subjects with >/= 4 fold rise in virus-specific serum IgA
Time frame: Day 1 to Day 45
Proportion of subjects with norovirus specific IgA-ASC/10^6 PBMC (freshly isolated PBMCs)
Time frame: Day 1 to Day 45
Proportion of subjects with norovirus specific IgG-ASC/10^6 PBMC (freshly isolated PBMCs)
Time frame: Day 1 to Day 45
Severity of diarrhea related to the challenge strain, determined using the Vesikari Score
Time frame: Day 1 to Day 5
Severity of vomiting related to the challenge strain, determined using the Vesikari Score
Time frame: Day 1 to Day 5
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2018.
- Derived from this study: PubMed 35137154Rouphael N, Beck A, Kirby AE, Liu P, Natrajan MS, Lai L, Phadke V, Winston J, Raabe V, Collins MH, Girmay T, Alvarez A, Beydoun N, Karmali V, Altieri-Rivera J, Lindesmith LC, Anderson EJ, Wang Y, El-Khorazaty J, Petrie C, Baric RS, Baqar S, Moe CL, Mulligan MJ. Dose-Response of a Norovirus GII.2 Controlled Human Challenge Model Inoculum. J Infect Dis. 2022 Nov 11;226(10):1771-1780. doi: 10.1093/infdis/jiac045.
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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.2 Challenge 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 10 inclusion and 24 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: finished, as of the sponsor's last update on 7 Dec 2018. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Infectious Dose-50 based on infection rate after challenge with various doses (time frame: Day 2 to Day 5). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02473224, which also lists 1 linked publication.
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 7 Dec 2018.