Trial Outcomes & Findings for Phase I Norovirus Challenge Model (NCT NCT04174560)
NCT ID: NCT04174560
Last Updated: 2025-03-06
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
48 participants
Primary outcome timeframe
Day 1 through Day 4
Results posted on
2025-03-06
Participant Flow
Participants were healthy non-pregnant adults, 18-49 years of age, inclusive. They were recruited from the community at large around the clinical site. Participants were enrolled between 28MAR2022 and 10JUL2023.
Participant milestones
| Measure |
3.5x10^3 Copies - Secretor Positive
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), on Day 1
Norovirus GII.4 Challenge Pool: 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.
|
3.5x10^4 Copies - Secretor Positive
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) on Day 1
Norovirus GII.4 Challenge Pool: 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.
|
3.5x10^5 Copies - Secretor Positive
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), on Day 1
Norovirus GII.4 Challenge Pool: 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.
|
Secretor Negative
Single dose (3.5x10\^3, 3.5x10\^4 or 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) given orally. Participants lacked the secretor gene.
Norovirus GII.4 Challenge Pool: 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.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
15
|
12
|
18
|
3
|
|
Overall Study
COMPLETED
|
14
|
12
|
16
|
3
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
2
|
0
|
Reasons for withdrawal
| Measure |
3.5x10^3 Copies - Secretor Positive
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), on Day 1
Norovirus GII.4 Challenge Pool: 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.
|
3.5x10^4 Copies - Secretor Positive
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) on Day 1
Norovirus GII.4 Challenge Pool: 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.
|
3.5x10^5 Copies - Secretor Positive
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), on Day 1
Norovirus GII.4 Challenge Pool: 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.
|
Secretor Negative
Single dose (3.5x10\^3, 3.5x10\^4 or 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) given orally. Participants lacked the secretor gene.
Norovirus GII.4 Challenge Pool: 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.
|
|---|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
2
|
0
|
Baseline Characteristics
Phase I Norovirus Challenge Model
Baseline characteristics by cohort
| Measure |
3.5x10^3 Copies - Secretor Positive
n=15 Participants
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) given orally. Participants tested positive for the secretor gene.
|
3.5x10^4 Copies - Secretor Positive
n=12 Participants
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) given orally. Participants tested positive for the secretor gene.
|
3.5x10^5 Copies - Secretor Positive
n=18 Participants
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) given orally. Participants tested positive for the secretor gene.
|
Secretor Negative
n=3 Participants
Single dose (3.5x10\^3, 3.5x10\^4 or 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) given orally. Participants lacked the secretor gene.
|
Total
n=48 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
37.4 years
STANDARD_DEVIATION 8.4 • n=5 Participants
|
35.2 years
STANDARD_DEVIATION 7.7 • n=7 Participants
|
35.3 years
STANDARD_DEVIATION 8.3 • n=5 Participants
|
36.7 years
STANDARD_DEVIATION 8.5 • n=4 Participants
|
36.0 years
STANDARD_DEVIATION 8.0 • n=21 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
26 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
22 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
13 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
45 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
15 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
32 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
15 participants
n=5 Participants
|
12 participants
n=7 Participants
|
18 participants
n=5 Participants
|
3 participants
n=4 Participants
|
48 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Day 1 through Day 4Population: Modified Intention-to-Treat Population: The mITT population includes all participants who received the challenge study product and contributed both pre- and at least one post-challenge sample during the inpatient period for which a conclusion can be made regarding illness and infectivity.
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.
Outcome measures
| Measure |
3.5x10^3 Copies - Secretor Positive
n=15 Participants
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) given orally
|
3.5x10^4 Copies - Secretor Positive
n=12 Participants
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) given orally
|
3.5x10^5 Copies - Secretor Positive
n=18 Participants
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) given orally
|
Secretor Negative
n=3 Participants
Single dose (3.5x10\^3, 3.5x10\^4 or 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) given orally. Participants lacked the secretor gene.
|
|---|---|---|---|---|
|
The Occurrence of Norovirus-associated Illness in Secretor Positive Participants Through Day 4 After Challenge.
|
3 Participants
|
2 Participants
|
7 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 1 through Day 10Population: Safety Population: The Safety Analysis population includes all participants who received at least a partial dose of the challenge study product.
Systemic solicited adverse events were collected pre-challenge, post-challenge, and via memory aid through 5 days after discharge from the isolation facility and graded on a scale of 0 (absent), 1 (mild), 2 (moderate) and 3 (severe). Systemic events include headache, nausea, abdominal cramps/discomfort/pain, abdominal gurgling, abdominal bloating, myalgia, malaise/fatigue, anorexia/loss of appetite, and chills.
Outcome measures
| Measure |
3.5x10^3 Copies - Secretor Positive
n=15 Participants
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) given orally
|
3.5x10^4 Copies - Secretor Positive
n=12 Participants
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) given orally
|
3.5x10^5 Copies - Secretor Positive
n=18 Participants
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) given orally
|
Secretor Negative
n=3 Participants
Single dose (3.5x10\^3, 3.5x10\^4 or 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) given orally. Participants lacked the secretor gene.
|
|---|---|---|---|---|
|
The Number of Participants With Solicited Adverse Events Through Day 10
|
10 Participants
|
10 Participants
|
15 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Day 1 through Day 180Population: Safety Population: The Safety Analysis population includes all participants who received at least a partial dose of the challenge study product.
An adverse event or suspected adverse reaction is considered "serious" if, in the view of either the investigator or sponsor, it results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization (excluding any extended stay during challenge admission due to continued vomiting, diarrhea, etc.), a persistent or significant incapacity of substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, important medical events that may not result in death, be life-threatening, or require hospitalizations may be considered serious when, based upon appropriate medical judgment they may jeopardize the patient or participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Outcome measures
| Measure |
3.5x10^3 Copies - Secretor Positive
n=15 Participants
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) given orally
|
3.5x10^4 Copies - Secretor Positive
n=12 Participants
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) given orally
|
3.5x10^5 Copies - Secretor Positive
n=18 Participants
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) given orally
|
Secretor Negative
n=3 Participants
Single dose (3.5x10\^3, 3.5x10\^4 or 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) given orally. Participants lacked the secretor gene.
|
|---|---|---|---|---|
|
The Number of Participants With Unsolicited Serious Adverse Events Reported Through Day 180.
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 1 through Day 30Population: Safety Population: The Safety Analysis population includes all participants who received at least a partial dose of the challenge study product.
ICH E6 defines an AE as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of medicinal (investigational) product. The FDA defines an AE as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.
Outcome measures
| Measure |
3.5x10^3 Copies - Secretor Positive
n=15 Participants
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) given orally
|
3.5x10^4 Copies - Secretor Positive
n=12 Participants
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) given orally
|
3.5x10^5 Copies - Secretor Positive
n=18 Participants
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) given orally
|
Secretor Negative
n=3 Participants
Single dose (3.5x10\^3, 3.5x10\^4 or 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) given orally. Participants lacked the secretor gene.
|
|---|---|---|---|---|
|
The Number of Participants With Unsolicited Grade 3 Adverse Events From Challenge to Day 30
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 1 through Day 30Population: Modified Intention-to-Treat Population: The mITT population includes all participants who received the challenge study product and contributed both pre- and at least one post-challenge sample during the inpatient period for which a conclusion can be made regarding illness and infectivity.
Detection of norovirus GII.4 in stool by qRT-PCR at Days 2, 3, 4, 5, 6, 15, or 30; or \>/= 4-fold rise from baseline in GII.4-specific antibody titers in serum IgG by ELISA through Day 30
Outcome measures
| Measure |
3.5x10^3 Copies - Secretor Positive
n=15 Participants
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) given orally
|
3.5x10^4 Copies - Secretor Positive
n=12 Participants
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) given orally
|
3.5x10^5 Copies - Secretor Positive
n=18 Participants
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) given orally
|
Secretor Negative
n=3 Participants
Single dose (3.5x10\^3, 3.5x10\^4 or 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) given orally. Participants lacked the secretor gene.
|
|---|---|---|---|---|
|
The Number of Participants With Infection Through Day 30
Detection of norovirus GII.4 in stool
|
4 Participants
|
4 Participants
|
9 Participants
|
0 Participants
|
|
The Number of Participants With Infection Through Day 30
>/= 4-fold rise in GII.4-specific antibody titers in serum IgG
|
3 Participants
|
4 Participants
|
9 Participants
|
1 Participants
|
|
The Number of Participants With Infection Through Day 30
Norovirus GII.4 in stool OR >/= 4-fold rise in GII.4-specific antibody titers in serum IgG
|
4 Participants
|
5 Participants
|
10 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Day 1 through Day 60Population: Modified Intention-to-Treat Population: The mITT population includes all participants who received the challenge study product and contributed both pre- and at least one post-challenge sample during the inpatient period for which a conclusion can be made regarding illness and infectivity, restricted to participants who were shedding on at least one day.
Peak virus in stool as measured by qRT-PCR \[genome equivalent copies per gram of stool (GEC/g)\] is the maximum GEC/g of all available stool samples tested post-challenge.
Outcome measures
| Measure |
3.5x10^3 Copies - Secretor Positive
n=4 Participants
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) given orally
|
3.5x10^4 Copies - Secretor Positive
n=4 Participants
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) given orally
|
3.5x10^5 Copies - Secretor Positive
n=9 Participants
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) given orally
|
Secretor Negative
Single dose (3.5x10\^3, 3.5x10\^4 or 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) given orally. Participants lacked the secretor gene.
|
|---|---|---|---|---|
|
Peak Genome Equivalent Copies/mL of Virus in Stool as Measured by qRT-PCR After Challenge Through Day 60
|
230475280.31 GEC/g
Interval 157130.618 to 338055406332.0
|
43569331.414 GEC/g
Interval 156752.339 to 12110100882.0
|
176337339.33 GEC/g
Interval 22259257.651 to 1396940442.9
|
—
|
SECONDARY outcome
Timeframe: Day 1 through Day 60Population: Modified Intention-to-Treat Population: The mITT population includes all participants who received the challenge study product and contributed both pre- and at least one post-challenge sample during the inpatient period for which a conclusion can be made regarding illness and infectivity, restricted to participants who were shedding on at least one day.
Duration is based on the first and last days where norovirus is detected.
Outcome measures
| Measure |
3.5x10^3 Copies - Secretor Positive
n=4 Participants
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) given orally
|
3.5x10^4 Copies - Secretor Positive
n=4 Participants
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) given orally
|
3.5x10^5 Copies - Secretor Positive
n=9 Participants
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) given orally
|
Secretor Negative
Single dose (3.5x10\^3, 3.5x10\^4 or 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) given orally. Participants lacked the secretor gene.
|
|---|---|---|---|---|
|
Duration (Number of Days) of Viral Secretion as Measured by qRT-PCR After Challenge Through Day 60
|
5 Days
Standard Deviation 2.7
|
9.8 Days
Standard Deviation 11.7
|
3.9 Days
Standard Deviation 1.5
|
—
|
SECONDARY outcome
Timeframe: Day 1 through Day 4Population: Modified Intention-to-Treat Population: The mITT population includes all participants who received the challenge study product and contributed both pre- and at least one post-challenge sample during the inpatient period for which a conclusion can be made regarding illness and infectivity.
The score is made up of the following components: duration of diarrhea (days), maximum number of diarrheal stools per 24 hours, duration of vomiting (days), maximum number of vomiting episodes per 24 hours, fever, and dehydration. Each of the components will be assigned a point value and the points will be summed to create a total score out of a possible 17 for each participant, with 17 being the worst outcome, and 0 being a better outcome.
Outcome measures
| Measure |
3.5x10^3 Copies - Secretor Positive
n=15 Participants
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) given orally
|
3.5x10^4 Copies - Secretor Positive
n=12 Participants
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) given orally
|
3.5x10^5 Copies - Secretor Positive
n=18 Participants
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) given orally
|
Secretor Negative
n=3 Participants
Single dose (3.5x10\^3, 3.5x10\^4 or 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) given orally. Participants lacked the secretor gene.
|
|---|---|---|---|---|
|
Modified Vesikari Score Through Day 4
|
2.5 Points on a scale
Standard Deviation 2.3
|
3.1 Points on a scale
Standard Deviation 2.2
|
3.8 Points on a scale
Standard Deviation 3.2
|
2.7 Points on a scale
Standard Deviation 1.5
|
SECONDARY outcome
Timeframe: Day 1 through Day 5Population: Modified Intention-to-Treat Population: The mITT population includes all participants who received the challenge study product and contributed both pre- and at least one post-challenge sample during the inpatient period for which a conclusion can be made regarding illness and infectivity. Participants included only experienced diarrhea and/or vomiting.
The duration of diarrhea will be calculated for participants who had at least three stools classified as having loose or watery consistency, or who have at least two stools classified as having loose or watery consistency with \> 300 gm of loose or watery stools in a study day (from 00:00 to 23:59). The duration will be calculated as the interval between the first time a loose/watery stool is produced on a day the participant met the criteria for diarrhea through the last loose/watery stool on a day the participant met the criteria for diarrhea. The duration of vomiting during the inpatient period will be calculated for participants who had at least two episodes of vomiting in a study day or over two consecutive days. The duration of diarrhea and/or vomiting will be calculated beginning from the first diarrheal stool or episode of vomiting until the last diarrheal stool or episode of vomiting during the inpatient period.
Outcome measures
| Measure |
3.5x10^3 Copies - Secretor Positive
n=2 Participants
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) given orally
|
3.5x10^4 Copies - Secretor Positive
n=3 Participants
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) given orally
|
3.5x10^5 Copies - Secretor Positive
n=7 Participants
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) given orally
|
Secretor Negative
n=2 Participants
Single dose (3.5x10\^3, 3.5x10\^4 or 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) given orally. Participants lacked the secretor gene.
|
|---|---|---|---|---|
|
Duration (Hours) of Vomiting and/or Diarrhea Through Day 5
Duration of Diarrhea
|
11.02 Hours
Standard Deviation 5.798
|
7.015 Hours
Standard Deviation 4.929
|
17.264 Hours
Standard Deviation 15.323
|
11.655 Hours
Standard Deviation 8.733
|
|
Duration (Hours) of Vomiting and/or Diarrhea Through Day 5
Duration of Vomiting
|
2.5 Hours
Standard Deviation NA
There was no standard deviation as only one participant experienced vomiting
|
6.62 Hours
Standard Deviation NA
There was no standard deviation as only one participant experienced vomiting
|
5.845 Hours
Standard Deviation 7.646
|
—
|
|
Duration (Hours) of Vomiting and/or Diarrhea Through Day 5
Duration of Diarrhea and/or Vomiting
|
11.37 Hours
Standard Deviation 6.293
|
6.883 Hours
Standard Deviation 3.492
|
15.937 Hours
Standard Deviation 13.38
|
11.655 Hours
Standard Deviation 8.733
|
Adverse Events
3.5x10^3 Copies - Secretor Positive
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
3.5x10^4 Copies - Secretor Positive
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
3.5x10^5 Copies - Secretor Positive
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Secretor Negative
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
3.5x10^3 Copies - Secretor Positive
n=15 participants at risk
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) given orally. Participants tested positive for the secretor gene.
|
3.5x10^4 Copies - Secretor Positive
n=12 participants at risk
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) given orally. Participants tested positive for the secretor gene.
|
3.5x10^5 Copies - Secretor Positive
n=18 participants at risk
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) given orally. Participants tested positive for the secretor gene.
|
Secretor Negative
n=3 participants at risk
Single dose (3.5x10\^3, 3.5x10\^4 or 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) given orally. Participants lacked the secretor gene.
|
|---|---|---|---|---|
|
Cardiac disorders
Bradycardia
|
6.7%
1/15 • Number of events 1 • Day 1 through Day 180
|
0.00%
0/12 • Day 1 through Day 180
|
5.6%
1/18 • Number of events 1 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
Cardiac disorders
Tachycardia
|
20.0%
3/15 • Number of events 3 • Day 1 through Day 180
|
0.00%
0/12 • Day 1 through Day 180
|
38.9%
7/18 • Number of events 7 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
Gastrointestinal disorders
Abdominal Pain Lower
|
0.00%
0/15 • Day 1 through Day 180
|
0.00%
0/12 • Day 1 through Day 180
|
5.6%
1/18 • Number of events 1 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
Gastrointestinal disorders
Diarrhoea
|
13.3%
2/15 • Number of events 2 • Day 1 through Day 180
|
8.3%
1/12 • Number of events 1 • Day 1 through Day 180
|
11.1%
2/18 • Number of events 3 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/15 • Day 1 through Day 180
|
0.00%
0/12 • Day 1 through Day 180
|
5.6%
1/18 • Number of events 1 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
Gastrointestinal disorders
Gastrointestinal Sounds Abnormal
|
40.0%
6/15 • Number of events 6 • Day 1 through Day 180
|
66.7%
8/12 • Number of events 8 • Day 1 through Day 180
|
72.2%
13/18 • Number of events 14 • Day 1 through Day 180
|
33.3%
1/3 • Number of events 1 • Day 1 through Day 180
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/15 • Day 1 through Day 180
|
0.00%
0/12 • Day 1 through Day 180
|
5.6%
1/18 • Number of events 1 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
General disorders
Chills
|
20.0%
3/15 • Number of events 3 • Day 1 through Day 180
|
25.0%
3/12 • Number of events 3 • Day 1 through Day 180
|
50.0%
9/18 • Number of events 9 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
General disorders
Fatigue
|
0.00%
0/15 • Day 1 through Day 180
|
8.3%
1/12 • Number of events 1 • Day 1 through Day 180
|
0.00%
0/18 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
General disorders
Pyrexia
|
6.7%
1/15 • Number of events 1 • Day 1 through Day 180
|
8.3%
1/12 • Number of events 1 • Day 1 through Day 180
|
5.6%
1/18 • Number of events 1 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
Infections and infestations
Bacterial Vaginosis
|
0.00%
0/15 • Day 1 through Day 180
|
0.00%
0/12 • Day 1 through Day 180
|
5.6%
1/18 • Number of events 1 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
Infections and infestations
Tooth Abscess
|
0.00%
0/15 • Day 1 through Day 180
|
0.00%
0/12 • Day 1 through Day 180
|
5.6%
1/18 • Number of events 1 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
Investigations
Blood Pressure Diastolic Decreased
|
0.00%
0/15 • Day 1 through Day 180
|
0.00%
0/12 • Day 1 through Day 180
|
5.6%
1/18 • Number of events 1 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
Investigations
Blood Pressure Diastolic Increased
|
6.7%
1/15 • Number of events 1 • Day 1 through Day 180
|
0.00%
0/12 • Day 1 through Day 180
|
5.6%
1/18 • Number of events 1 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
Investigations
Blood Pressure Systolic Decreased
|
6.7%
1/15 • Number of events 1 • Day 1 through Day 180
|
0.00%
0/12 • Day 1 through Day 180
|
0.00%
0/18 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
Investigations
Blood Pressure Systolic Increased
|
6.7%
1/15 • Number of events 1 • Day 1 through Day 180
|
0.00%
0/12 • Day 1 through Day 180
|
0.00%
0/18 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
Metabolism and nutrition disorders
Dehydration
|
6.7%
1/15 • Number of events 1 • Day 1 through Day 180
|
0.00%
0/12 • Day 1 through Day 180
|
0.00%
0/18 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
6.7%
1/15 • Number of events 1 • Day 1 through Day 180
|
0.00%
0/12 • Day 1 through Day 180
|
0.00%
0/18 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
Nervous system disorders
Dizziness
|
6.7%
1/15 • Number of events 1 • Day 1 through Day 180
|
0.00%
0/12 • Day 1 through Day 180
|
0.00%
0/18 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
Nervous system disorders
Syncope
|
0.00%
0/15 • Day 1 through Day 180
|
0.00%
0/12 • Day 1 through Day 180
|
5.6%
1/18 • Number of events 1 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
6.7%
1/15 • Number of events 1 • Day 1 through Day 180
|
0.00%
0/12 • Day 1 through Day 180
|
0.00%
0/18 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
Gastrointestinal disorders
Abdominal Distension
|
40.0%
6/15 • Number of events 6 • Day 1 through Day 180
|
58.3%
7/12 • Number of events 7 • Day 1 through Day 180
|
38.9%
7/18 • Number of events 7 • Day 1 through Day 180
|
33.3%
1/3 • Number of events 1 • Day 1 through Day 180
|
|
Gastrointestinal disorders
Abdominal Pain
|
46.7%
7/15 • Number of events 7 • Day 1 through Day 180
|
66.7%
8/12 • Number of events 8 • Day 1 through Day 180
|
50.0%
9/18 • Number of events 9 • Day 1 through Day 180
|
33.3%
1/3 • Number of events 1 • Day 1 through Day 180
|
|
Gastrointestinal disorders
Nausea
|
40.0%
6/15 • Number of events 6 • Day 1 through Day 180
|
50.0%
6/12 • Number of events 6 • Day 1 through Day 180
|
61.1%
11/18 • Number of events 11 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
General disorders
Malaise
|
33.3%
5/15 • Number of events 5 • Day 1 through Day 180
|
75.0%
9/12 • Number of events 9 • Day 1 through Day 180
|
50.0%
9/18 • Number of events 9 • Day 1 through Day 180
|
66.7%
2/3 • Number of events 2 • Day 1 through Day 180
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
13.3%
2/15 • Number of events 2 • Day 1 through Day 180
|
50.0%
6/12 • Number of events 6 • Day 1 through Day 180
|
44.4%
8/18 • Number of events 8 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
20.0%
3/15 • Number of events 3 • Day 1 through Day 180
|
33.3%
4/12 • Number of events 4 • Day 1 through Day 180
|
44.4%
8/18 • Number of events 8 • Day 1 through Day 180
|
0.00%
0/3 • Day 1 through Day 180
|
|
Nervous system disorders
Headache
|
46.7%
7/15 • Number of events 7 • Day 1 through Day 180
|
50.0%
6/12 • Number of events 6 • Day 1 through Day 180
|
61.1%
11/18 • Number of events 11 • Day 1 through Day 180
|
33.3%
1/3 • Number of events 1 • Day 1 through Day 180
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60