Trial Outcomes & Findings for Cell Mediated Immunity Against RSV and Influenza in a Human Experimental Challenge (NCT NCT02755948)
NCT ID: NCT02755948
Last Updated: 2024-12-06
Results Overview
Total Symptom Score in infected versus uninfected participants by Jackson's criteria. Eight symptoms were evaluated in the symptom diary: nasal discharge, nasal congestion, sneezing, cough, sore throat, headache, feverishness and fatigue. Subjects were asked to score each symptom 0 (absent), 1 (mild), 2 (moderate), 3 (severe). A clinical cold was defined as 2 out of 3 of: a cumulative 14-day symptom score of ≥14; a subjective feeling of a cold; nasal discharge for ≥3 days. Symptoms were evaluated over a longer period than in Jackson's original description to account for an anticipated slower onset and longer duration of illness with RSV compared with rhinovirus. Maximum cumulative symptom score is therefore 336.
COMPLETED
NA
75 participants
14 days
2024-12-06
Participant Flow
Participant milestones
| Measure |
RSV A Memphis 37
Participants will be inoculated with RSV Memphis 37 virus.
RSV A Memphis 37: Good Manufacturing Practices-certified RSV Memphis 37 10(4) PFU in 1 mL 25% sucrose/DMEM delivered by intranasal drops
|
Influenza A/California/04/2009-like (H1N1)
Participants will be inoculated with Influenza A/California/04/2009-like (H1N1).
Influenza A/California/04/2009-likw (H1N1): Good Manufacturing Practices-certified Influenza A/California/04/09 3.5x10\^6 TCID50 in 1 mL in DPBS delivered by intranasal drops
|
Influenza A/Belgium/4217/2015 (H3N2)
Participants will be inoculated with Influenza A/Belgium/4217/2015 (H3N2).
Influenza A/Belgium/4217/2015 (H3N2): Good Manufacturing Practices-certified Influenza A/Belgium/4217/2015 (H3N2) 3.5x10\^6 TCID50 in 1 mL in DPBS delivered by intranasal drops
|
|---|---|---|---|
|
Overall Study
STARTED
|
41
|
24
|
10
|
|
Overall Study
COMPLETED
|
41
|
24
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Cell Mediated Immunity Against RSV and Influenza in a Human Experimental Challenge
Baseline characteristics by cohort
| Measure |
RSV A Memphis 37
n=41 Participants
Participants will be inoculated with RSV Memphis 37 virus.
RSV A Memphis 37: Good Manufacturing Practices-certified RSV Memphis 37 10(4) PFU in 1 mL 25% sucrose/DMEM delivered by intranasal drops
|
Influenza A/California/04/2009-like (H1N1)
n=24 Participants
Participants will be inoculated with Influenza A/California/04/2009-like (H1N1).
Influenza A/California/04/2009-likw (H1N1): Good Manufacturing Practices-certified Influenza A/California/04/09 3.5x10\^6 TCID50 in 1 mL in DPBS delivered by intranasal drops
|
Influenza A/Belgium/4217/2015 (H3N2)
n=10 Participants
Participants will be inoculated with Influenza A/Belgium/4217/2015 (H3N2).
Influenza A/Belgium/4217/2015 (H3N2): Good Manufacturing Practices-certified Influenza A/Belgium/4217/2015 (H3N2) 3.5x10\^6 TCID50 in 1 mL in DPBS delivered by intranasal drops
|
Total
n=75 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
41 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
75 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Continuous
|
26.2 years
n=5 Participants
|
45.3 years
n=7 Participants
|
37.2 years
n=5 Participants
|
33.8 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
29 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
52 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White British
|
0 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
19 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian or Asian British (other)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White (other)
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian or Asian British (Pakistan)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Mixed (White & Caribbean)
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
All other ethnic groups
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White Irish
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or Black British (Caribbean)
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian or Asian British (Indian)
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or Black British (African)
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
41 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
41 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Mixed White (White & Asian)
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Region of Enrollment
United Kingdom
|
41 participants
n=5 Participants
|
24 participants
n=7 Participants
|
10 participants
n=5 Participants
|
75 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 14 daysPopulation: Total number of participants challenged with the specified challenge virus. For the H1N1 arm, only 22 out of 24 participants were analysed because one participant lost their symptom diary and another was excluded from analysis as they had RSV co-infection
Total Symptom Score in infected versus uninfected participants by Jackson's criteria. Eight symptoms were evaluated in the symptom diary: nasal discharge, nasal congestion, sneezing, cough, sore throat, headache, feverishness and fatigue. Subjects were asked to score each symptom 0 (absent), 1 (mild), 2 (moderate), 3 (severe). A clinical cold was defined as 2 out of 3 of: a cumulative 14-day symptom score of ≥14; a subjective feeling of a cold; nasal discharge for ≥3 days. Symptoms were evaluated over a longer period than in Jackson's original description to account for an anticipated slower onset and longer duration of illness with RSV compared with rhinovirus. Maximum cumulative symptom score is therefore 336.
Outcome measures
| Measure |
RSV A Memphis 37
n=41 Participants
Participants will be inoculated with RSV Memphis 37 virus.
RSV A Memphis 37: Good Manufacturing Practices-certified RSV Memphis 37 10(4) PFU in 1 mL 25% sucrose/DMEM delivered by intranasal drops
|
Influenza A/California/04/2009-like (H1N1)
n=22 Participants
Participants will be inoculated with Influenza A/California/04/2009-like (H1N1).
Influenza A/California/04/2009-likw (H1N1): Good Manufacturing Practices-certified Influenza A/California/04/09 3.5x10\^6 TCID50 in 1 mL in DPBS delivered by intranasal drops
|
Influenza A/Belgium/4217/2015 (H3N2)
n=10 Participants
Participants will be inoculated with Influenza A/Belgium/4217/2015 (H3N2).
Influenza A/Belgium/4217/2015 (H3N2): Good Manufacturing Practices-certified Influenza A/Belgium/4217/2015 (H3N2) 3.5x10\^6 TCID50 in 1 mL in DPBS delivered by intranasal drops
|
|---|---|---|---|
|
Total Symptom Score
Infected
|
29.25 score on a scale
Interval 8.5 to 47.5
|
17.50 score on a scale
Interval 8.75 to 23.0
|
11.00 score on a scale
Interval 7.5 to 18.75
|
|
Total Symptom Score
Uninfected
|
13.00 score on a scale
Interval 4.75 to 22.0
|
0 score on a scale
Interval 0.0 to 1.25
|
1 score on a scale
Interval 0.0 to 4.0
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: For the H1N1 arm, one participant was excluded from analysis as they had RSV co-infection. For the RSV arm, only 32/41 participants were analysed because there were insufficient PBMCs from the remaining participants to run the analysis
Peak Ki-67+ CD38+ CD8+ T cells in the blood by flow cytometry.
Outcome measures
| Measure |
RSV A Memphis 37
n=32 Participants
Participants will be inoculated with RSV Memphis 37 virus.
RSV A Memphis 37: Good Manufacturing Practices-certified RSV Memphis 37 10(4) PFU in 1 mL 25% sucrose/DMEM delivered by intranasal drops
|
Influenza A/California/04/2009-like (H1N1)
n=23 Participants
Participants will be inoculated with Influenza A/California/04/2009-like (H1N1).
Influenza A/California/04/2009-likw (H1N1): Good Manufacturing Practices-certified Influenza A/California/04/09 3.5x10\^6 TCID50 in 1 mL in DPBS delivered by intranasal drops
|
Influenza A/Belgium/4217/2015 (H3N2)
n=7 Participants
Participants will be inoculated with Influenza A/Belgium/4217/2015 (H3N2).
Influenza A/Belgium/4217/2015 (H3N2): Good Manufacturing Practices-certified Influenza A/Belgium/4217/2015 (H3N2) 3.5x10\^6 TCID50 in 1 mL in DPBS delivered by intranasal drops
|
|---|---|---|---|
|
Frequency of T Cells in Blood by Flow Cytometry
Infected
|
0.79 % of CD8+ lymphocytes
Interval 0.42 to 1.1
|
3.81 % of CD8+ lymphocytes
Interval 2.46 to 5.56
|
4.13 % of CD8+ lymphocytes
Interval 2.55 to 16.21
|
|
Frequency of T Cells in Blood by Flow Cytometry
Uninfected
|
0.49 % of CD8+ lymphocytes
Interval 0.24 to 0.81
|
0.985 % of CD8+ lymphocytes
Interval 0.752 to 1.535
|
1.18 % of CD8+ lymphocytes
Interval 0.77 to 1.59
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: For the H1N1 arm, one participant was excluded from analysis as they had RSV co-infection. For the RSV arm, only 20/41 participants were analysed because there were insufficient airway cells from some participants to run the analysis. For the H3N2 arm, the analysis was not run on the 3 uninfected participants. Only 3 were analysed in the infected participants because 1 participant was excluded for co-infection and the other 3 participants had insufficient airway cells to run the analysis.
Peak Ki-67+ CD38+ CD8+ T cells in bronchoalveolar lavage (BAL) by flow cytometry
Outcome measures
| Measure |
RSV A Memphis 37
n=20 Participants
Participants will be inoculated with RSV Memphis 37 virus.
RSV A Memphis 37: Good Manufacturing Practices-certified RSV Memphis 37 10(4) PFU in 1 mL 25% sucrose/DMEM delivered by intranasal drops
|
Influenza A/California/04/2009-like (H1N1)
n=23 Participants
Participants will be inoculated with Influenza A/California/04/2009-like (H1N1).
Influenza A/California/04/2009-likw (H1N1): Good Manufacturing Practices-certified Influenza A/California/04/09 3.5x10\^6 TCID50 in 1 mL in DPBS delivered by intranasal drops
|
Influenza A/Belgium/4217/2015 (H3N2)
n=3 Participants
Participants will be inoculated with Influenza A/Belgium/4217/2015 (H3N2).
Influenza A/Belgium/4217/2015 (H3N2): Good Manufacturing Practices-certified Influenza A/Belgium/4217/2015 (H3N2) 3.5x10\^6 TCID50 in 1 mL in DPBS delivered by intranasal drops
|
|---|---|---|---|
|
Frequency of T Cells in Respiratory Tract by Flow Cytometry
Infected
|
2.21 % of CD8+ lymphocytes
Interval 0.96 to 3.8
|
81.15 % of CD8+ lymphocytes
Interval 0.0 to 90.48
|
4.36 % of CD8+ lymphocytes
Interval 1.35 to 5.49
|
|
Frequency of T Cells in Respiratory Tract by Flow Cytometry
Uninfected
|
0.65 % of CD8+ lymphocytes
Interval 0.27 to 1.11
|
0.412 % of CD8+ lymphocytes
Interval 0.187 to 0.598
|
—
|
SECONDARY outcome
Timeframe: 28 daysPopulation: For the H1N1 arm, one participant was excluded from analysis as they had RSV co-infection.
Nasal wash viral load by quantitative polymerase chain reaction (qPCR) (Area under curve)
Outcome measures
| Measure |
RSV A Memphis 37
n=41 Participants
Participants will be inoculated with RSV Memphis 37 virus.
RSV A Memphis 37: Good Manufacturing Practices-certified RSV Memphis 37 10(4) PFU in 1 mL 25% sucrose/DMEM delivered by intranasal drops
|
Influenza A/California/04/2009-like (H1N1)
n=23 Participants
Participants will be inoculated with Influenza A/California/04/2009-like (H1N1).
Influenza A/California/04/2009-likw (H1N1): Good Manufacturing Practices-certified Influenza A/California/04/09 3.5x10\^6 TCID50 in 1 mL in DPBS delivered by intranasal drops
|
Influenza A/Belgium/4217/2015 (H3N2)
n=10 Participants
Participants will be inoculated with Influenza A/Belgium/4217/2015 (H3N2).
Influenza A/Belgium/4217/2015 (H3N2): Good Manufacturing Practices-certified Influenza A/Belgium/4217/2015 (H3N2) 3.5x10\^6 TCID50 in 1 mL in DPBS delivered by intranasal drops
|
|---|---|---|---|
|
Viral Load
Infected
|
18.24 log10 copies*days/mL
Interval 11.51 to 24.34
|
5.85 log10 copies*days/mL
Interval 0.82 to 9.22
|
26.40 log10 copies*days/mL
Interval 5.52 to 33.13
|
|
Viral Load
Uninfected
|
0 log10 copies*days/mL
Interval 0.0 to 0.0
|
0 log10 copies*days/mL
Interval 0.0 to 0.0
|
0 log10 copies*days/mL
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: For the H1N1 arm, there were only enough remaining PBMCs from 14 participants. For the H3N2 arm, there were insufficient cells to run the analysis. For the RSV arm, only 18/41 participants were analysed because there were insufficient PBMCs from the remaining participants to run the analysis.
Peak T cells in blood by Enzyme-linked Immunospot (ELISpot). IFNy SFU/million PBMCs (Spot Forming Unit)
Outcome measures
| Measure |
RSV A Memphis 37
n=18 Participants
Participants will be inoculated with RSV Memphis 37 virus.
RSV A Memphis 37: Good Manufacturing Practices-certified RSV Memphis 37 10(4) PFU in 1 mL 25% sucrose/DMEM delivered by intranasal drops
|
Influenza A/California/04/2009-like (H1N1)
n=14 Participants
Participants will be inoculated with Influenza A/California/04/2009-like (H1N1).
Influenza A/California/04/2009-likw (H1N1): Good Manufacturing Practices-certified Influenza A/California/04/09 3.5x10\^6 TCID50 in 1 mL in DPBS delivered by intranasal drops
|
Influenza A/Belgium/4217/2015 (H3N2)
Participants will be inoculated with Influenza A/Belgium/4217/2015 (H3N2).
Influenza A/Belgium/4217/2015 (H3N2): Good Manufacturing Practices-certified Influenza A/Belgium/4217/2015 (H3N2) 3.5x10\^6 TCID50 in 1 mL in DPBS delivered by intranasal drops
|
|---|---|---|---|
|
Frequency of T Cells in Blood by Enzyme-linked Immunospot (ELISpot)
Infected
|
778.30 IFNy SFU/million PBMCs
Interval 459.2 to 1228.0
|
161 IFNy SFU/million PBMCs
Interval 128.0 to 214.0
|
—
|
|
Frequency of T Cells in Blood by Enzyme-linked Immunospot (ELISpot)
Uninfected
|
159.20 IFNy SFU/million PBMCs
Interval 43.75 to 419.2
|
29 IFNy SFU/million PBMCs
Interval 21.0 to 43.0
|
—
|
Adverse Events
RSV A Memphis 37
Influenza A/California/04/2009-like (H1N1)
Influenza A/Belgium/4217/2015 (H3N2)
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place