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H1N1v Virus Challenge Study in Healthy Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04044352
Recruitment Status : Completed
First Posted : August 5, 2019
Results First Posted : April 28, 2021
Last Update Posted : April 28, 2021
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Basic Science
Condition Influenza
Intervention Biological: Influenza A/Bethesda/MM2/H1N1 Challenge
Enrollment 76
Recruitment Details Healthy adults, male and female, between the ages of 18 and 49, who are non-habitual smokers without medical conditions at high risk for severe complications of influenza virus infection were enrolled. Participants were enrolled between 22OCT2019 and 05DEC2019.
Pre-assignment Details  
Arm/Group Title Study Group
Hide Arm/Group Description Participants will receive 2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Period Title: Overall Study
Started 76
Completed 65
Not Completed 11
Reason Not Completed
Lost to Follow-up             9
Withdrawal by Subject             2
Arm/Group Title Study Group
Hide Arm/Group Description Participants will receive 2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Baseline Participants 76
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 76 participants
<=18 years
0
   0.0%
Between 18 and 65 years
76
 100.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 76 participants
33.4  (9.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 76 participants
Female
30
  39.5%
Male
46
  60.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 76 participants
Hispanic or Latino
5
   6.6%
Not Hispanic or Latino
71
  93.4%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 76 participants
American Indian or Alaska Native
1
   1.3%
Asian
1
   1.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
35
  46.1%
White
34
  44.7%
More than one race
3
   3.9%
Unknown or Not Reported
2
   2.6%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 76 participants
76
 100.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 76 participants
Saint Louis University
17
  22.4%
Cincinnati Children's Hospital
24
  31.6%
University of Maryland
20
  26.3%
Duke University
15
  19.7%
Receipt of Prior Seasonal Influenza Vaccination (2018-2019)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 76 participants
Yes
9
  11.8%
No
67
  88.2%
Receipt of Prior Non-Seasonal Influenza Vaccination (2018-2019)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 76 participants
Yes
3
   3.9%
No
73
  96.1%
Baseline Seroprotection (Hemagglutination Inhibition)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 76 participants
Low < 1:40
39
  51.3%
High >= 1:40
37
  48.7%
Baseline Seroprotection (Microneutralization)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 76 participants
Low < 1:40
23
  30.3%
High >= 1:40
53
  69.7%
1.Primary Outcome
Title Percentage of Healthy Participants Reporting Mild-to-Moderate Influenza Disease (MMID) by Baseline A/Bethesda/MM2/H1N1 Hemagglutination Inhibition (HAI) Antibody Seroprotection Status (Titer >/= 1:40 vs. Titer < 1:40)
Hide Description Blood samples were collected pre-challenge (Day -2) for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated from available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). MMID is a composite endpoint determined by the presence of viral shedding (detected by any approved positive RT-PCR test from a NP swab), accompanied by at least one the following symptoms occurring any time from Day 2 through Day 8; body aches or pain, chest tightness, chills, conjunctivitis, nasal congestion, sinus congestion, coryza, decreased appetite, diarrhea, dry cough, dyspnea, fatigue, fever, headache, lymphopenia, nausea, a 3% or more decrease in oxygen saturation from baseline, productive cough, rhinorrhea, sore throat, and sweats. The percentage of participants that developed MMID was calculated within each pre-challenge seroprotection status group.
Time Frame Day 2 through Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had a baseline sample for immunogenicity, and were followed for the entire duration of the study challenge period, or at least until MMID was observed.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Measure Type: Number
Unit of Measure: percentage of participants
Baseline Seroprotection Status Low < 1:40 : MMID Number Analyzed 39 participants
77
Baseline Seroprotection Status Low < 1:40 : No MMID Number Analyzed 39 participants
23
Baseline Seroprotection Status High > = 1:40 : MMID Number Analyzed 37 participants
65
Baseline Seroprotection Status High > = 1:40 : No MMID Number Analyzed 37 participants
35
2.Primary Outcome
Title Association Between Clinical or Laboratory Manifestation of MMID and A/Bethesda/MM2/H1N1 HAI Antibodies in Serum at Baseline
Hide Description Blood samples were collected pre-challenge (Day -2) for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated from available results. MMID is a composite endpoint determined by the presence of viral shedding (detected by any approved positive RT-PCR test from a NP swab), accompanied by at least one the following symptoms occurring any time from Day 2 through Day 8; body aches or pain, chest tightness, chills, conjunctivitis, nasal congestion, sinus congestion, coryza, decreased appetite, diarrhea, dry cough, dyspnea, fatigue, fever, headache, lymphopenia, nausea, a 3% or more decrease in oxygen saturation from baseline, productive cough, rhinorrhea, sore throat, and sweats. The relationship between the level of pre-challenge HAI titer and the likelihood of developing MMID during the study challenge period (Day 2 to Day 8) was assessed via logistic regression.
Time Frame Day 2 to Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had a baseline sample for immunogenicity, and were followed for the entire duration of the study challenge period, or at least until MMID was observed.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Measure Type: Number
Unit of Measure: Odds Ratio
0.81
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Study Group
Comments Pre-challenge (baseline) HAI geometric mean titer was log-2 transformed and treated as a continuous variable in the model.
Type of Statistical Test Other
Comments Likelihood ratio test was the statistical test.
Statistical Test of Hypothesis P-Value 0.126
Comments [Not Specified]
Method Wald Chi-Square
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.62 to 1.06
Estimation Comments A two-fold increase in HAI pre-challenge titer (i.e. one unit increase in log-2 titer) corresponds to a 19% decrease in the odds of developing MMID during the study challenge period (Day 2 through Day 8).
3.Secondary Outcome
Title Geometric Mean Titer (GMT) of HAI Antibody in Serum at Baseline by Infection Status
Hide Description Blood samples were collected pre-challenge (Day -2) and post-challenge on Days 8, 29 and 61 for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated from available results. The geometric mean across samples was calculated within each study day and by infection status as observed over the study challenge period (Day 2 to Day 8); RT-PCR Negative (never positive), RT-PCR Positive Asymptomatic (participants with at least one positive PCR result but no symptoms reported), at least once RT-PCR Positive Symptomatic (or MMID).
Time Frame Day -2
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had an available immunogenicity sample for the given study day, and were followed for the entire duration of the study challenge period, or at least until MMID was observed.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Geometric Mean (95% Confidence Interval)
Unit of Measure: titer
RT-PCR Positive Symptomatic Number Analyzed 54 participants
36.8
(26.1 to 52.0)
RT-PCR Positive Asymptomatic Number Analyzed 8 participants
20.0
(6.9 to 58.0)
RT-PCR Negative Number Analyzed 14 participants
117.9
(61.3 to 227.0)
4.Secondary Outcome
Title GMT of HAI Antibody in Serum at Day 8 by Infection Status
Hide Description Blood samples were collected pre-challenge (Day -2) and post-challenge on Days 8, 29 and 61 for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated from available results. The geometric mean across samples was calculated within each study day and by infection status as observed over the study challenge period (Day 2 to Day 8); RT-PCR Negative (never positive), RT-PCR Positive Asymptomatic (participants with at least one positive PCR result but no symptoms reported), at least once RT-PCR Positive Symptomatic (or MMID).
Time Frame Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had an available immunogenicity sample for the given study day, and were followed for the entire duration of the study challenge period, or at least until MMID was observed.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 75
Geometric Mean (95% Confidence Interval)
Unit of Measure: titer
RT-PCR Positive Symptomatic Number Analyzed 53 participants
46.1
(33.2 to 64.0)
RT-PCR Positive Asymptomatic Number Analyzed 8 participants
23.7
(8.9 to 63.1)
RT-PCR Negative Number Analyzed 14 participants
122.5
(66.9 to 224.6)
5.Secondary Outcome
Title GMT of HAI Antibody in Serum at Day 29 by Infection Status
Hide Description Blood samples were collected pre-challenge (Day -2) and post-challenge on Days 8, 29 and 61 for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated from available results. The geometric mean across samples was calculated within each study day and by infection status as observed over the study challenge period (Day 2 to Day 8); RT-PCR Negative (never positive), RT-PCR Positive Asymptomatic (participants with at least one positive PCR result but no symptoms reported), at least once RT-PCR Positive Symptomatic (or MMID).
Time Frame Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had an available immunogenicity sample for the given study day, and were followed for the entire duration of the study challenge period, or at least until MMID was observed.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 67
Geometric Mean (95% Confidence Interval)
Unit of Measure: titer
RT-PCR Positive Symptomatic Number Analyzed 46 participants
87.4
(65.7 to 116.2)
RT-PCR Positive Asymptomatic Number Analyzed 7 participants
63.9
(29.2 to 139.9)
RT-PCR Negative Number Analyzed 14 participants
126.6
(72.3 to 221.9)
6.Secondary Outcome
Title GMT of HAI Antibody in Serum at Day 61 by Infection Status
Hide Description Blood samples were collected pre-challenge (Day -2) and post-challenge on Days 8, 29 and 61 for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated from available results. The geometric mean across samples was calculated within each study day and by infection status as observed over the study challenge period (Day 2 to Day 8); RT-PCR Negative (never positive), RT-PCR Positive Asymptomatic (participants with at least one positive PCR result but no symptoms reported), at least once RT-PCR Positive Symptomatic (or MMID).
Time Frame Day 61
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had an available immunogenicity sample for the given study day, and were followed for the entire duration of the study challenge period, or at least until MMID was observed
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 62
Geometric Mean (95% Confidence Interval)
Unit of Measure: titer
RT-PCR Positive Symptomatic Number Analyzed 43 participants
78.0
(55.5 to 109.7)
RT-PCR Positive Asymptomatic Number Analyzed 6 participants
71.3
(33.6 to 151.1)
RT-PCR Negative Number Analyzed 13 participants
123.1
(63.9 to 237.3)
7.Secondary Outcome
Title Percentage of Healthy Participants Achieving HAI Seroconversion From Baseline in Serum at Day 8 by Infection Status
Hide Description Blood samples were collected pre-challenge (Day -2) and post-challenge on Days 8, 29 and 61 for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. Seroconversion was defined as a pre-challenge titer 1:10 or greater and a minimum 4-fold rise in post-challenge antibody titer. The percentage of participants achieving seroconversion was calculated within each post-challenge study day and by infection status as observed over the study challenge period (Day 2 to Day 8); RT-PCR Negative (never positive), RT-PCR Positive Asymptomatic (participants with at least one positive PCR result but no symptoms reported), at least once RT-PCR Positive Symptomatic (or MMID).
Time Frame Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had an available immunogenicity sample for the given study day, and were followed for the entire duration of the study challenge period, or at least until MMID was observed
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 75
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
RT-PCR Positive Symptomatic Number Analyzed 53 participants
3.8
(0.5 to 13)
RT-PCR Positive Asymptomatic Number Analyzed 8 participants
0
(0 to 36.9)
RT-PCR Negative Number Analyzed 14 participants
0
(0 to 23.2)
8.Secondary Outcome
Title Percentage of Healthy Participants Achieving HAI Seroconversion in Serum From Baseline at Day 29 by Infection Status
Hide Description Blood samples were collected pre-challenge (Day -2) and post-challenge on Days 8, 29 and 61 for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. Seroconversion was defined as a pre-challenge titer 1:10 or greater and a minimum 4-fold rise in post-challenge antibody titer. The percentage of participants achieving seroconversion was calculated within each post-challenge study day and by infection status as observed over the study challenge period (Day 2 to Day 8); RT-PCR Negative (never positive), RT-PCR Positive Asymptomatic (participants with at least one positive PCR result but no symptoms reported), at least once RT-PCR Positive Symptomatic (or MMID).
Time Frame Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had an available immunogenicity sample for the given study day, and were followed for the entire duration of the study challenge period, or at least until MMID was observed
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 67
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
RT-PCR Positive Symptomatic Number Analyzed 46 participants
28.3
(16 to 43.5)
RT-PCR Positive Asymptomatic Number Analyzed 7 participants
28.6
(3.7 to 71)
RT-PCR Negative Number Analyzed 14 participants
0
(0 to 23.2)
9.Secondary Outcome
Title Percentage of Healthy Participants Achieving HAI Seroconversion in Serum From Baseline at Day 61 by Infection Status
Hide Description Blood samples were collected pre-challenge (Day -2) and post-challenge on Days 8, 29 and 61 for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. Seroconversion was defined as a pre-challenge titer 1:10 or greater and a minimum 4-fold rise in post-challenge antibody titer. The percentage of participants achieving seroconversion was calculated within each post-challenge study day and by infection status as observed over the study challenge period (Day 2 to Day 8); RT-PCR Negative (never positive), RT-PCR Positive Asymptomatic (participants with at least one positive PCR result but no symptoms reported), at least once RT-PCR Positive Symptomatic (or MMID).
Time Frame Day 61
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had an available immunogenicity sample for the given study day, and were followed for the entire duration of the study challenge period, or at least until MMID was observed
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 62
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
RT-PCR Positive Symptomatic Number Analyzed 43 participants
18.6
(8.4 to 33.4)
RT-PCR Positive Asymptomatic Number Analyzed 6 participants
33.3
(4.3 to 77.7)
RT-PCR Negative Number Analyzed 13 participants
0
(0 to 24.7)
10.Secondary Outcome
Title GMT of Microneutralization (MN) Antibody in Serum at Baseline by Infection Status
Hide Description Blood samples were collected pre-challenge (Day -2) and post-challenge on Days 8, 29 and 61 for the MN assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated from available results. The geometric mean across samples was calculated within each study day and by infection status as observed over the study challenge period (Day 2 to Day 8); RT-PCR Negative (never positive), RT-PCR Positive Asymptomatic (participants with at least one positive PCR result but no symptoms reported), at least once RT-PCR Positive Symptomatic (or MMID).
Time Frame Day -2
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had an available immunogenicity sample for the given study day, and were followed for the entire duration of the study challenge period, or at least until MMID was observed
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Geometric Mean (95% Confidence Interval)
Unit of Measure: titer
RT-PCR Positive Symptomatic Number Analyzed 54 participants
62.9
(43.1 to 91.9)
RT-PCR Positive Asymptomatic Number Analyzed 8 participants
44.3
(13.8 to 142.6)
RT-PCR Negative Number Analyzed 14 participants
276.7
(124.8 to 613.1)
11.Secondary Outcome
Title GMT of MN Antibody in Serum at Day 8 by Infection Status
Hide Description Blood samples were collected pre-challenge (Day -2) and post-challenge on Days 8, 29 and 61 for the MN assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated from available results. The geometric mean across samples was calculated within each study day and by infection status as observed over the study challenge period (Day 2 to Day 8); RT-PCR Negative (never positive), RT-PCR Positive Asymptomatic (participants with at least one positive PCR result but no symptoms reported), at least once RT-PCR Positive Symptomatic (or MMID).
Time Frame Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had an available immunogenicity sample for the given study day, and were followed for the entire duration of the study challenge period, or at least until MMID was observed
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 75
Geometric Mean (95% Confidence Interval)
Unit of Measure: titer
RT-PCR Positive Symptomatic Number Analyzed 53 participants
87.7
(61.7 to 124.6)
RT-PCR Positive Asymptomatic Number Analyzed 8 participants
52.4
(16.6 to 165.5)
RT-PCR Negative Number Analyzed 14 participants
250.6
(112.8 to 556.9)
12.Secondary Outcome
Title GMT of MN Antibody in Serum at Day 29 by Infection Status
Hide Description Blood samples were collected pre-challenge (Day -2) and post-challenge on Days 8, 29 and 61 for the MN assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated from available results. The geometric mean across samples was calculated within each study day and by infection status as observed over the study challenge period (Day 2 to Day 8); RT-PCR Negative (never positive), RT-PCR Positive Asymptomatic (participants with at least one positive PCR result but no symptoms reported), at least once RT-PCR Positive Symptomatic (or MMID).
Time Frame Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had an available immunogenicity sample for the given study day, and were followed for the entire duration of the study challenge period, or at least until MMID was observed
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 67
Geometric Mean (95% Confidence Interval)
Unit of Measure: titer
RT-PCR Positive Symptomatic Number Analyzed 46 participants
159.5
(115.7 to 220.1)
RT-PCR Positive Asymptomatic Number Analyzed 7 participants
103.1
(41.5 to 255.9)
RT-PCR Negative Number Analyzed 14 participants
320.0
(157.9 to 648.5)
13.Secondary Outcome
Title GMT of MN Antibody in Serum at Day 61 by Infection Status
Hide Description Blood samples were collected pre-challenge (Day -2) and post-challenge on Days 8, 29 and 61 for the MN assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated from available results. The geometric mean across samples was calculated within each study day and by infection status as observed over the study challenge period (Day 2 to Day 8); RT-PCR Negative (never positive), RT-PCR Positive Asymptomatic (participants with at least one positive PCR result but no symptoms reported), at least once RT-PCR Positive Symptomatic (or MMID).
Time Frame Day 61
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had an available immunogenicity sample for the given study day, and were followed for the entire duration of the study challenge period, or at least until MMID was observed
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 62
Geometric Mean (95% Confidence Interval)
Unit of Measure: titer
RT-PCR Positive Symptomatic (MMID-1) Number Analyzed 43 participants
151.8
(108.7 to 211.9)
RT-PCR Positive Asymptomatic Number Analyzed 6 participants
107.2
(30.4 to 377.8)
RT-PCR Negative Number Analyzed 13 participants
287.6
(134.9 to 613.2)
14.Secondary Outcome
Title Percentage of Healthy Participants Achieving MN Seroconversion From Baseline in Serum at Day 8 by Infection Status
Hide Description Blood samples were collected pre-challenge (Day -2) and post-challenge on Days 8, 29 and 61 for the MN assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. Seroconversion was defined as a pre-challenge titer 1:10 or greater and a minimum 4-fold rise in post-challenge antibody titer. The percentage of participants achieving seroconversion was calculated within each post-challenge study day and by infection status as observed over the study challenge period (Day 2 to Day 8); RT-PCR Negative (never positive), RT-PCR Positive Asymptomatic (participants with at least one positive PCR result but no symptoms reported), at least once RT-PCR Positive Symptomatic (or MMID).
Time Frame Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had an available immunogenicity sample for the given study day, and were followed for the entire duration of the study challenge period, or at least until MMID was observed
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 75
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
RT-PCR Positive Symptomatic Number Analyzed 53 participants
7.5
(2.1 to 18.2)
RT-PCR Positive Asymptomatic Number Analyzed 8 participants
0
(0 to 36.9)
RT-PCR Negative Number Analyzed 14 participants
0
(0 to 23.2)
15.Secondary Outcome
Title Percentage of Healthy Participants Achieving MN Seroconversion From Baseline in Serum at Day 29 by Infection Status
Hide Description Blood samples were collected pre-challenge (Day -2) and post-challenge on Days 8, 29 and 61 for the MN assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. Seroconversion was defined as a pre-challenge titer 1:10 or greater and a minimum 4-fold rise in post-challenge antibody titer. The percentage of participants achieving seroconversion was calculated within each post-challenge study day and by infection status as observed over the study challenge period (Day 2 to Day 8); RT-PCR Negative (never positive), RT-PCR Positive Asymptomatic (participants with at least one positive PCR result but no symptoms reported), at least once RT-PCR Positive Symptomatic (or MMID).
Time Frame Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had an available immunogenicity sample for the given study day, and were followed for the entire duration of the study challenge period, or at least until MMID was observed
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 67
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
RT-PCR Positive Symptomatic Number Analyzed 46 participants
26.1
(14.3 to 41.1)
RT-PCR Positive Asymptomatic Number Analyzed 7 participants
28.6
(3.7 to 71)
RT-PCR Negative Number Analyzed 14 participants
0
(0 to 23.2)
16.Secondary Outcome
Title Percentage of Healthy Participants Achieving MN Seroconversion From Baseline in Serum at Day 61 by Infection Status
Hide Description Blood samples were collected pre-challenge (Day -2) and post-challenge on Days 8, 29 and 61 for the MN assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. Seroconversion was defined as a pre-challenge titer 1:10 or greater and a minimum 4-fold rise in post-challenge antibody titer. The percentage of participants achieving seroconversion was calculated within each post-challenge study day and by infection status as observed over the study challenge period (Day 2 to Day 8); RT-PCR Negative (never positive), RT-PCR Positive Asymptomatic (participants with at least one positive PCR result but no symptoms reported), at least once RT-PCR Positive Symptomatic (or MMID).
Time Frame Day 61
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had an available immunogenicity sample for the given study day, and were followed for the entire duration of the study challenge period, or at least until MMID was observed
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 62
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
RT-PCR Positive Symptomatic Number Analyzed 43 participants
18.6
(8.4 to 33.4)
RT-PCR Positive Asymptomatic Number Analyzed 6 participants
50
(11.8 to 88.2)
RT-PCR Negative Number Analyzed 13 participants
0
(0 to 24.7)
17.Secondary Outcome
Title Duration of Viral Shedding in Nasopharyngeal (NP) Swab by Baseline HAI Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated from available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). Duration of viral shedding (detected by any approved positive RT-PCR test from NP swab) was calculated from the day of the initial positive PCR result to the day of the last positive PCR result prior to discharge from the challenge unit facility, regardless of intermittent negative PCR results. The mean duration of viral shedding was calculated among participants with detected virus within each pre-challenge HAI seroprotection status group.
Time Frame Day 2 through Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had a baseline sample for immunogenicity, and were followed for the entire duration of the study challenge period.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 61
Mean (95% Confidence Interval)
Unit of Measure: days
Low < 1:40 Number Analyzed 35 participants
3.8
(2.9 to 4.7)
High >= 1:40 Number Analyzed 26 participants
2.3
(1.6 to 3.0)
18.Secondary Outcome
Title Duration of Viral Shedding in NP Swab by Baseline MN Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the MN assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated from available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). Duration of viral shedding (detected by any approved positive RT-PCR test from NP swab) was calculated from the day of the initial positive PCR result to the day of the last positive PCR result prior to discharge from the challenge unit facility, regardless of intermittent negative PCR results. The mean duration of viral shedding was calculated among participants with detected virus within each pre-challenge MN seroprotection status group.
Time Frame Day 2 to Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had a baseline sample for immunogenicity, and were followed for the entire duration of the study challenge period.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 75
Mean (95% Confidence Interval)
Unit of Measure: Days
Low < 1:40 Number Analyzed 23 participants
3.9
(2.6 to 5.2)
High >= 1:40 Number Analyzed 52 participants
2.7
(2.1 to 3.3)
19.Secondary Outcome
Title Number of Participants With Viral Shedding in NP Swab at Day 2 by Baseline HAI Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated for available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). The number of participants with viral shedding (detected by any approved positive RT-PCR test from a NP swab) was calculated for each study day post-challenge (Day 2 to Day 8) and at any time during the entire challenge period within each pre-challenge seroprotection status group.
Time Frame Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge with available results.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Measure Type: Count of Participants
Unit of Measure: Participants
Low < 1:40 Number Analyzed 39 participants
35
  89.7%
High >= 1:40 Number Analyzed 37 participants
25
  67.6%
20.Secondary Outcome
Title Number of Participants With Viral Shedding in NP Swab at Day 3 by Baseline HAI Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated for available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). The number of participants with viral shedding (detected by any approved positive RT-PCR test from a NP swab) was calculated for each study day post-challenge (Day 2 to Day 8) and at any time during the entire challenge period within each pre-challenge seroprotection status group.
Time Frame Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge with available results.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Measure Type: Count of Participants
Unit of Measure: Participants
Low < 1:40 Number Analyzed 39 participants
27
  69.2%
High >= 1:40 Number Analyzed 37 participants
11
  29.7%
21.Secondary Outcome
Title Number of Participants With Viral Shedding in NP Swab at Day 4 by Baseline HAI Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated for available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). The number of participants with viral shedding (detected by any approved positive RT-PCR test from a NP swab) was calculated for each study day post-challenge (Day 2 to Day 8) and at any time during the entire challenge period within each pre-challenge seroprotection status group.
Time Frame Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge with available results.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Measure Type: Count of Participants
Unit of Measure: Participants
Low < 1:40 Number Analyzed 39 participants
18
  46.2%
High >= 1:40 Number Analyzed 37 participants
7
  18.9%
22.Secondary Outcome
Title Number of Participants With Viral Shedding in NP Swab at Day 5 by Baseline HAI Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated for available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). The number of participants with viral shedding (detected by any approved positive RT-PCR test from a NP swab) was calculated for each study day post-challenge (Day 2 to Day 8) and at any time during the entire challenge period within each pre-challenge seroprotection status group.
Time Frame Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge with available results.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Measure Type: Count of Participants
Unit of Measure: Participants
Low < 1:40 Number Analyzed 39 participants
15
  38.5%
High >= 1:40 Number Analyzed 37 participants
0
   0.0%
23.Secondary Outcome
Title Number of Participants With Viral Shedding in NP Swab at Day 6 by Baseline HAI Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated for available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). The number of participants with viral shedding (detected by any approved positive RT-PCR test from a NP swab) was calculated for each study day post-challenge (Day 2 to Day 8) and at any time during the entire challenge period within each pre-challenge seroprotection status group.
Time Frame Day 6
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge with available results.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Measure Type: Count of Participants
Unit of Measure: Participants
Low < 1:40 Number Analyzed 39 participants
12
  30.8%
High >= 1:40 Number Analyzed 37 participants
3
   8.1%
24.Secondary Outcome
Title Number of Participants With Viral Shedding in NP Swab at Day 7 by Baseline HAI Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated for available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). The number of participants with viral shedding (detected by any approved positive RT-PCR test from a NP swab) was calculated for each study day post-challenge (Day 2 to Day 8) and at any time during the entire challenge period within each pre-challenge seroprotection status group.
Time Frame Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge with available results.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Measure Type: Count of Participants
Unit of Measure: Participants
Low < 1:40 Number Analyzed 39 participants
9
  23.1%
High >= 1:40 Number Analyzed 37 participants
1
   2.7%
25.Secondary Outcome
Title Number of Participants With Viral Shedding in NP Swab at Day 8 by Baseline HAI Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated for available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). The number of participants with viral shedding (detected by any approved positive RT-PCR test from a NP swab) was calculated for each study day post-challenge (Day 2 to Day 8) and at any time during the entire challenge period within each pre-challenge seroprotection status group.
Time Frame Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge with available results.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 75
Measure Type: Count of Participants
Unit of Measure: Participants
Low < 1:40 Number Analyzed 38 participants
5
  13.2%
High >= 1:40 Number Analyzed 37 participants
1
   2.7%
26.Secondary Outcome
Title Number of Participants With Viral Shedding in NP Swab Anytime Post-challenge by Baseline HAI Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated for available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). The number of participants with viral shedding (detected by any approved positive RT-PCR test from a NP swab) was calculated for each study day post-challenge (Day 2 to Day 8) and at any time during the entire challenge period within each pre-challenge seroprotection status group.
Time Frame Day 2 to Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge with available results.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Measure Type: Count of Participants
Unit of Measure: Participants
Low < 1:40 Number Analyzed 39 participants
36
  92.3%
High >= 1:40 Number Analyzed 37 participants
26
  70.3%
27.Secondary Outcome
Title Number of Participants With Viral Shedding in NP Swab at Day 2 by Baseline MN Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the MN assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated for available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). The number of participants with viral shedding (detected by any approved positive RT-PCR test from a NP swab) was calculated for each study day post-challenge (Day 2 to Day 8) and at any time during the entire challenge period within each pre-challenge seroprotection status group.
Time Frame Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge with available results.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Measure Type: Count of Participants
Unit of Measure: Participants
Low < 1:40 Number Analyzed 23 participants
21
  91.3%
High >= 1:40 Number Analyzed 53 participants
39
  73.6%
28.Secondary Outcome
Title Number of Participants With Viral Shedding in NP Swab at Day 3 by Baseline MN Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the MN assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated for available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). The number of participants with viral shedding (detected by any approved positive RT-PCR test from a NP swab) was calculated for each study day post-challenge (Day 2 to Day 8) and at any time during the entire challenge period within each pre-challenge seroprotection status group.
Time Frame Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge with available results.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Measure Type: Count of Participants
Unit of Measure: Participants
Low < 1:40 Number Analyzed 23 participants
16
  69.6%
High >= 1:40 Number Analyzed 53 participants
22
  41.5%
29.Secondary Outcome
Title Number of Participants With Viral Shedding in NP Swab at Day 4 by Baseline MN Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the MN assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated for available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). The number of participants with viral shedding (detected by any approved positive RT-PCR test from a NP swab) was calculated for each study day post-challenge (Day 2 to Day 8) and at any time during the entire challenge period within each pre-challenge seroprotection status group.
Time Frame Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge with available results.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Measure Type: Count of Participants
Unit of Measure: Participants
Low < 1:40 Number Analyzed 23 participants
10
  43.5%
High >= 1:40 Number Analyzed 53 participants
15
  28.3%
30.Secondary Outcome
Title Number of Participants With Viral Shedding in NP Swab at Day 5 by Baseline MN Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the MN assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated for available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). The number of participants with viral shedding (detected by any approved positive RT-PCR test from a NP swab) was calculated for each study day post-challenge (Day 2 to Day 8) and at any time during the entire challenge period within each pre-challenge seroprotection status group.
Time Frame Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge with available results.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Measure Type: Count of Participants
Unit of Measure: Participants
Low < 1:40 Number Analyzed 23 participants
9
  39.1%
High >= 1:40 Number Analyzed 53 participants
6
  11.3%
31.Secondary Outcome
Title Number of Participants With Viral Shedding in NP Swab at Day 6 by Baseline MN Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the MN assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated for available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). The number of participants with viral shedding (detected by any approved positive RT-PCR test from a NP swab) was calculated for each study day post-challenge (Day 2 to Day 8) and at any time during the entire challenge period within each pre-challenge seroprotection status group.
Time Frame Day 6
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge with available results.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Measure Type: Count of Participants
Unit of Measure: Participants
Low < 1:40 Number Analyzed 23 participants
8
  34.8%
High >= 1:40 Number Analyzed 53 participants
7
  13.2%
32.Secondary Outcome
Title Number of Participants With Viral Shedding in NP Swab at Day 7 by Baseline MN Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the MN assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated for available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). The number of participants with viral shedding (detected by any approved positive RT-PCR test from a NP swab) was calculated for each study day post-challenge (Day 2 to Day 8) and at any time during the entire challenge period within each pre-challenge seroprotection status group.
Time Frame Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge with available results.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Measure Type: Count of Participants
Unit of Measure: Participants
Low < 1:40 Number Analyzed 23 participants
6
  26.1%
High >= 1:40 Number Analyzed 53 participants
4
   7.5%
33.Secondary Outcome
Title Number of Participants With Viral Shedding in NP Swab at Day 8 by Baseline MN Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the MN assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated for available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). The number of participants with viral shedding (detected by any approved positive RT-PCR test from a NP swab) was calculated for each study day post-challenge (Day 2 to Day 8) and at any time during the entire challenge period within each pre-challenge seroprotection status group.
Time Frame Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge with available results.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 75
Measure Type: Count of Participants
Unit of Measure: Participants
Low < 1:40 Number Analyzed 23 participants
5
  21.7%
High >= 1:40 Number Analyzed 52 participants
1
   1.9%
34.Secondary Outcome
Title Number of Participants With Viral Shedding in NP Swab Anytime Post-challenge by Baseline MN Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated for available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). The number of participants with viral shedding (detected by any approved positive RT-PCR test from a NP swab) was calculated for each study day post-challenge (Day 2 to Day 8) and at any time during the entire challenge period within each pre-challenge seroprotection status group.
Time Frame Day 2 through Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge with available results.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Measure Type: Count of Participants
Unit of Measure: Participants
Low < 1:40 Number Analyzed 23 participants
22
  95.7%
High >= 1:40 Number Analyzed 53 participants
40
  75.5%
35.Secondary Outcome
Title Time Until Detectable Viral Shedding in NP Swab by Baseline HAI Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated from available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). Time until viral shedding (detected by any approved positive RT-PCR test from a NP swab) was calculated as the initial day of viral shedding post-challenge for each participant. Median time to viral shedding was calculated within each pre-challenge seroprotection status group via the Kaplan-Meier estimator.
Time Frame Day 2 through Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had a baseline sample for immunogenicity, and were followed for the entire duration of the study challenge period, or at least until viral shedding was observed.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Median (95% Confidence Interval)
Unit of Measure: Days
Low < 1:40 Number Analyzed 39 participants
2.0 [1] 
(NA to NA)
High >= 1:40 Number Analyzed 37 participants
2.0 [1] 
(NA to NA)
All Subjects Number Analyzed 76 participants
2.0 [1] 
(NA to NA)
[1]
Not calculable due to insufficient variability
36.Secondary Outcome
Title Time Until Detectable Viral Shedding in NP Swab by Baseline MN Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the MN assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated from available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). Time until viral shedding (detected by any approved positive RT-PCR test from a NP swab) was calculated as the initial day of viral shedding post-challenge for each participant. Median time to viral shedding was calculated within each pre-challenge seroprotection status group via the Kaplan-Meier estimator.
Time Frame Day 2 through Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had a baseline sample for immunogenicity, and were followed for the entire duration of the study challenge period, or at least until viral shedding was observed.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1 challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Median (95% Confidence Interval)
Unit of Measure: Days
Low < 1:40 Number Analyzed 23 participants
2.0 [1] 
(NA to NA)
High >= 1:40 Number Analyzed 53 participants
2.0 [1] 
(NA to NA)
[1]
Not calculable due to insufficient variability
37.Secondary Outcome
Title Magnitude of Viral Shedding in NP Swab by Baseline HAI Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated from available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). The quantity of viral load copies/mL from NP swab was measured via quantitative RT-PCR result for each post-challenge study day. The mean of each sample's quantitative PCR replicate results was calculated from available results. Total viral shedding, as observed until study discharge, was calculated as the area under the curve (AUC), then log-10 transformed. Peak viral shedding was calculated as the maximum viral load copies/mL observed until study discharge, then log-10 transformed. The mean and median of the log-10 AUC and the mean and median of the log-10 peak viral load were both calculated within each pre-challenge seroprotection status group.
Time Frame Day 2 through Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had a baseline sample for immunogenicity, were followed for the entire duration of the study challenge period,.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 75
Mean (Full Range)
Unit of Measure: log-10 copies/mL
Peak viral load - Low < 1:40 Number Analyzed 38 participants
4.7
(-1.5 to 14.8)
Peak viral load - High >= 1:40 Number Analyzed 37 participants
2.1
(-1.2 to 11.6)
AUC - Low < 1:40 Number Analyzed 38 participants
4.7
(-2.2 to 14.8)
AUC - High >= 1:40 Number Analyzed 37 participants
1.8
(-1.7 to 11.6)
38.Secondary Outcome
Title Magnitude of Viral Shedding in NP Swab by Baseline MN Seroprotection Status
Hide Description Blood samples were collected pre-challenge (Day -2) for the MN assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated from available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). The quantity of viral load copies/mL from NP swab was measured via quantitative RT-PCR result for each post-challenge study day. The mean of each sample's quantitative PCR replicate results was calculated from available results. Total viral shedding, as observed until study discharge, was calculated as the area under the curve (AUC), then log-10 transformed. Peak viral shedding was calculated as the maximum viral load copies/mL observed until study discharge, then log-10 transformed. The mean and median of the log-10 AUC and the mean and median of the log-10 peak viral load were both calculated within each pre-challenge seroprotection status group.
Time Frame Day 2 through Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge, had a baseline sample for immunogenicity, and were followed for the entire duration of the study challenge period.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 75
Mean (Full Range)
Unit of Measure: log-10 copies/mL
Peak viral load - Low < 1:40 Number Analyzed 23 participants
4.7
(-1.5 to 14.8)
Peak viral load - High >= 1:40 Number Analyzed 52 participants
2.9
(-1.4 to 12.1)
AUC - Low < 1:40 Number Analyzed 23 participants
4.6
(-2.2 to 14.8)
AUC - High >= 1:40 Number Analyzed 52 participants
2.7
(-2.1 to 12.2)
39.Secondary Outcome
Title Percentage of Participants Reporting Any MMID Symptom During Challenge Period by Viral Shedding Status and Baseline HAI Seroprotection Status From Serum Measured at Baseline - RT-PCR Positive (One or More)
Hide Description Blood samples were collected pre-challenge (Day -2) for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated from available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). The presence of any of the following symptoms was assessed from Day 2 to Day 8; body aches or pain, chest tightness, chills, conjunctivitis, nasal congestion, sinus congestion, coryza, decreased appetite, diarrhea, dry cough, dyspnea, fatigue, fever, headache, lymphopenia, nausea, a 3% or more decrease in oxygen saturation from baseline, productive cough, rhinorrhea, sore throat, and sweats. The percentage of participants that reported any symptom was calculated within each pre-challenge seroprotection status group and by viral shedding status, as observed anytime from Day 2 to Day 8; RT-PCR Negative (never positive), and at least once RT-PCR Positive.
Time Frame Day 2 through Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
All RT-PCR Positive (one or more) participants who received the study challenge, had a baseline sample for immunogenicity, and were followed for the entire duration of the study challenge period.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 62
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Any Symptom: Low < 1:40 Number Analyzed 36 participants
83.3
(67.2 to 93.6)
Any Symptom: High >= 1:40 Number Analyzed 26 participants
92.3
(74.9 to 99.1)
40.Secondary Outcome
Title Percentage of Participants Reporting Any MMID Symptom During Challenge Period by Viral Shedding Status and Baseline HAI Seroprotection Status From Serum Measured at Baseline With RT-PCR Negative (None Positive)
Hide Description Blood samples were collected pre-challenge (Day -2) for the HAI assay conducted with the A/Bethesda/MM2/H1N1 virus as the antigen. The geometric mean of each sample's replicate results was calculated from available results, then grouped by seroprotection status (titer results >= 1:40 vs < 1:40). The presence of any of the following symptoms was assessed from Day 2 to Day 8; body aches or pain, chest tightness, chills, conjunctivitis, nasal congestion, sinus congestion, coryza, decreased appetite, diarrhea, dry cough, dyspnea, fatigue, fever, headache, lymphopenia, nausea, a 3% or more decrease in oxygen saturation from baseline, productive cough, rhinorrhea, sore throat, and sweats. The percentage of participants that reported any symptom was calculated within each pre-challenge seroprotection status group and by viral shedding status, as observed anytime from Day 2 to Day 8; RT-PCR Negative (never positive), and at least once RT-PCR Positive.
Time Frame Day 2 through Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
All RT-PCR Negative (none positive) participants who received the study challenge, had a baseline sample for immunogenicity, and were followed for the entire duration of the study challenge period.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 14
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Any Symptom: Low < 1:40 Number Analyzed 3 participants
100
(29.2 to 100)
Any Symptom: High >= 1:40 Number Analyzed 11 participants
100
(71.5 to 100)
41.Secondary Outcome
Title Number of Serious Adverse Events (SAE) Post-challenge Through the Inpatient Stay
Hide Description SAEs included any untoward medical occurrence that resulted in death or a congenital anomaly/birth defect; was life threatening or a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation of existing hospitalization. All events are included regardless of relationship to the study challenge.
Time Frame Day 1 through Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge.
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
42.Secondary Outcome
Title Number of Serious Adverse Events (SAE) Post- Inpatient Discharge Through the Duration of the Study
Hide Description SAEs included any untoward medical occurrence that resulted in death or a congenital anomaly/birth defect; was life threatening or a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation of existing hospitalization. All events are included regardless of relationship to the study challenge.This table provides the number and percentage of participants who reported SAEs following discharge from the study hospital.
Time Frame Day 9 through Day 91
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received the study challenge
Arm/Group Title Study Group
Hide Arm/Group Description:
2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1challenge virus administered intranasally via a sprayer on Day 1.
Overall Number of Participants Analyzed 76
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
Time Frame All adverse events (AEs) that occurred from Receipt of Vaccination (Day 1) through final study visit (Day 91 +/- 7 days) were reported.
Adverse Event Reporting Description Solicited AEs were assessed using MedDRA 22.0
 
Arm/Group Title Group 1
Hide Arm/Group Description

2 mL (approximately 5x10^6/mL tissue culture infective dose (TCID50)) of influenza A/Bethesda/MM2/H1N1challenge virus administered intranasally via a sprayer on Day 1. N=80.

Influenza A/Bethesda/MM2/H1N1 Challenge: Reverse-genetics derived live A/California/04/2009/H1N1-like influenza virus passaged six times in Vero cells.

All-Cause Mortality
Group 1
Affected / at Risk (%)
Total   0/76 (0.00%)    
Hide Serious Adverse Events
Group 1
Affected / at Risk (%) # Events
Total   0/76 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Group 1
Affected / at Risk (%) # Events
Total   41/76 (53.95%)    
Blood and lymphatic system disorders   
Lymphadenopathy * 1  10/76 (13.16%)  10
Cardiac disorders   
Tachycardia * 1  8/76 (10.53%)  8
Infections and infestations   
Upper Respiratory Tract Infection * 1  5/76 (6.58%)  5
Investigations   
Alanine Aminotransferase Increased * 1  7/76 (9.21%)  11
Blood Pressure Diastolic Decreased * 1  5/76 (6.58%)  8
Blood Pressure Increased * 1  4/76 (5.26%)  4
Blood Pressure Systolic Increased * 1  9/76 (11.84%)  15
Platelet Count Increased * 1  7/76 (9.21%)  14
Respiratory Rate Increased * 1  6/76 (7.89%)  9
1
Term from vocabulary, MedDRA (22.0)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Kathleen M. Neuzil, MD, MPH
Organization: University of Maryland School of Medicine
Phone: 410-706-4946
EMail: kneuzil@som.umaryland.edu
Layout table for additonal information
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT04044352    
Other Study ID Numbers: 18-0010
HHSN272201300015I
First Submitted: August 1, 2019
First Posted: August 5, 2019
Results First Submitted: February 25, 2021
Results First Posted: April 28, 2021
Last Update Posted: April 28, 2021