Trial Outcomes & Findings for Experimental Human Pneumococcal Challenge With SPN3 (NCT NCT05535868)
NCT ID: NCT05535868
Last Updated: 2026-06-29
Results Overview
The proportion of participants with experimental SPN3 colonisation of the nasopharynx, determined by SPN3 presence in classical microbiological culture in at least one nasal wash (NW) sample, at any time point following one or two inoculations (combined and individually). This will be assessed for each isolate and dose separately.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
91 participants
Primary outcome timeframe
From inoculation (day 0) to the final visit for each participant (28 days post-inoculation)
Results posted on
2026-06-29
Participant Flow
4 participants excluded from intervention due to natural carriage of pneumococcus at screening. 1 participant discontinued after intervention due to antibiotics given for separate illness, before primary outcome data could be collected. Per protocol enrolment n=91; mITT analysis n=86.
Participant milestones
| Measure |
MLW-10V, 10000 CFU/ml
Malawi isolate, low dose
|
MLW-10V, 20000 CFU/ml
Malawi isolate, intermediate dose
|
MLW-10V, 80000 CFU/ml
Malawi isolate, higher dose
|
LIV014-S3, 10000 CFU/ml
Liverpool isolate, low dose
|
LIV014-S3, 20000 CFU/ml
Liverpool isolate, intermediate dose
|
LIV014-S3, 80000 CFU/ml
Liverpool isolate, higher dose (includes dose-ranging and reproducibility study participants, since the reproducibility study only included this isolate and dose)
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
9
|
10
|
10
|
7
|
10
|
40
|
|
Overall Study
Day 2 post-inoculation
|
9
|
10
|
10
|
7
|
10
|
40
|
|
Overall Study
Day 7 post-inoculation
|
9
|
10
|
10
|
7
|
10
|
40
|
|
Overall Study
Day 13 post-inoculation
|
9
|
10
|
10
|
7
|
10
|
40
|
|
Overall Study
Day 16 post-inoculation
|
9
|
10
|
10
|
7
|
10
|
40
|
|
Overall Study
Day 21 post-inoculation
|
9
|
10
|
10
|
7
|
10
|
40
|
|
Overall Study
Day 28 post-inoculation
|
9
|
10
|
10
|
7
|
10
|
40
|
|
Overall Study
COMPLETED
|
9
|
10
|
10
|
7
|
10
|
40
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Experimental Human Pneumococcal Challenge With SPN3
Baseline characteristics by cohort
| Measure |
LIV014-S3, 80000 CFU/ml
n=40 Participants
Liverpool isolate, higher dose (includes dose-ranging and reproducibility study participants, since the reproducibility study only included this isolate and dose)
|
Total
n=86 Participants
Total of all reporting groups
|
MLW-10V, 10000 CFU/ml
n=9 Participants
Malawi isolate, low dose
|
MLW-10V, 20000 CFU/ml
n=10 Participants
Malawi isolate, intermediate dose
|
MLW-10V, 80000 CFU/ml
n=10 Participants
Malawi isolate, higher dose
|
LIV014-S3, 10000 CFU/ml
n=7 Participants
Liverpool isolate, low dose
|
LIV014-S3, 20000 CFU/ml
n=10 Participants
Liverpool isolate, intermediate dose
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
24 Years
n=22 Participants
|
22 Years
n=23 Participants
|
28 Years
n=9 Participants
|
20 Years
n=27 Participants
|
20 Years
n=267 Participants
|
28 Years
n=265 Participants
|
21 Years
n=568 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=22 Participants
|
57 Participants
n=23 Participants
|
7 Participants
n=9 Participants
|
6 Participants
n=27 Participants
|
8 Participants
n=267 Participants
|
5 Participants
n=265 Participants
|
9 Participants
n=568 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=22 Participants
|
29 Participants
n=23 Participants
|
2 Participants
n=9 Participants
|
4 Participants
n=27 Participants
|
2 Participants
n=267 Participants
|
2 Participants
n=265 Participants
|
1 Participants
n=568 Participants
|
|
Race/Ethnicity, Customized
Asian
|
9 Participants
n=22 Participants
|
12 Participants
n=23 Participants
|
0 Participants
n=9 Participants
|
2 Participants
n=27 Participants
|
0 Participants
n=267 Participants
|
0 Participants
n=265 Participants
|
1 Participants
n=568 Participants
|
|
Race/Ethnicity, Customized
Black
|
1 Participants
n=22 Participants
|
2 Participants
n=23 Participants
|
0 Participants
n=9 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=267 Participants
|
0 Participants
n=265 Participants
|
0 Participants
n=568 Participants
|
|
Race/Ethnicity, Customized
Other
|
2 Participants
n=22 Participants
|
7 Participants
n=23 Participants
|
0 Participants
n=9 Participants
|
1 Participants
n=27 Participants
|
0 Participants
n=267 Participants
|
1 Participants
n=265 Participants
|
3 Participants
n=568 Participants
|
|
Race/Ethnicity, Customized
White
|
28 Participants
n=22 Participants
|
65 Participants
n=23 Participants
|
9 Participants
n=9 Participants
|
7 Participants
n=27 Participants
|
9 Participants
n=267 Participants
|
6 Participants
n=265 Participants
|
6 Participants
n=568 Participants
|
PRIMARY outcome
Timeframe: From inoculation (day 0) to the final visit for each participant (28 days post-inoculation)Population: Table shows cumulative proportion of participants with experimental colonisation following prime inoculation by day 13 post-inoculation (1st row) and following targeted booster inoculation by day 28 post-prime inoculation (second row)
The proportion of participants with experimental SPN3 colonisation of the nasopharynx, determined by SPN3 presence in classical microbiological culture in at least one nasal wash (NW) sample, at any time point following one or two inoculations (combined and individually). This will be assessed for each isolate and dose separately.
Outcome measures
| Measure |
MLW-10V, 10000 CFU/ml
n=9 Participants
Malawi isolate, low dose
|
MLW-10V, 20000 CFU/ml
n=10 Participants
Malawi isolate, intermediate dose
|
MLW-10V, 80000 CFU/ml
n=10 Participants
Malawi isolate, higher dose
|
LIV014-S3, 10000 CFU/ml
n=7 Participants
Liverpool isolate, low dose
|
LIV014-S3, 20000 CFU/ml
n=10 Participants
Liverpool isolate, intermediate dose
|
LIV014-S3, 80000 CFU/ml
n=40 Participants
Liverpool isolate, higher dose (includes dose-ranging and reproducibility study participants, since the reproducibility study only included this isolate and dose)
|
|---|---|---|---|---|---|---|
|
To Determine the Optimal SPN3 Dose and Isolate to Establish Colonisation of the Nasopharynx in Healthy Adults
Rate of experimental colonisation after prime inoculation · Experimental colonisation following targeted booster inoculation
|
4 Participants
|
1 Participants
|
6 Participants
|
1 Participants
|
4 Participants
|
28 Participants
|
|
To Determine the Optimal SPN3 Dose and Isolate to Establish Colonisation of the Nasopharynx in Healthy Adults
Rate of experimental colonisation after prime inoculation · Negative for experimental colonisation after targeted booster inoculation
|
5 Participants
|
9 Participants
|
4 Participants
|
6 Participants
|
6 Participants
|
12 Participants
|
|
To Determine the Optimal SPN3 Dose and Isolate to Establish Colonisation of the Nasopharynx in Healthy Adults
Rate of experimental colonisation after targeted booster · Experimental colonisation following targeted booster inoculation
|
5 Participants
|
2 Participants
|
8 Participants
|
1 Participants
|
8 Participants
|
34 Participants
|
|
To Determine the Optimal SPN3 Dose and Isolate to Establish Colonisation of the Nasopharynx in Healthy Adults
Rate of experimental colonisation after targeted booster · Negative for experimental colonisation after targeted booster inoculation
|
4 Participants
|
8 Participants
|
2 Participants
|
6 Participants
|
2 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: From inoculation (day 0) to the final visit for each participant (28 days post-inoculation)Population: Density table is log10 geometric mean CFU/ml and its range, across all timepoints combined, for participants positive for experimental colonisation at any and all timepoints. Variation in colonisation density across the study timepoints is reported in study publication (pending).
The bacterial density of experimental SPN3 colonisation of the nasopharynx in NW, at each and any time point following one or two inoculations (combined and individually), determined by classical microbiological culture, assessed for each isolate and dose separately. The number of participants analysed includes only the participants who developed SPN3 colonisation in each arm/group, rather than the total number of participants inoculated.
Outcome measures
| Measure |
MLW-10V, 10000 CFU/ml
n=5 Participants
Malawi isolate, low dose
|
MLW-10V, 20000 CFU/ml
n=2 Participants
Malawi isolate, intermediate dose
|
MLW-10V, 80000 CFU/ml
n=8 Participants
Malawi isolate, higher dose
|
LIV014-S3, 10000 CFU/ml
n=1 Participants
Liverpool isolate, low dose
|
LIV014-S3, 20000 CFU/ml
n=8 Participants
Liverpool isolate, intermediate dose
|
LIV014-S3, 80000 CFU/ml
n=34 Participants
Liverpool isolate, higher dose (includes dose-ranging and reproducibility study participants, since the reproducibility study only included this isolate and dose)
|
|---|---|---|---|---|---|---|
|
To Determine the Density of Experimental SPN3 Colonisation of the Nasopharynx.
|
100 Colony forming units per millilitre
Interval 10.0 to 1000.0
|
50 Colony forming units per millilitre
Interval 1.0 to 175.0
|
300 Colony forming units per millilitre
Interval 100.0 to 1000.0
|
1 Colony forming units per millilitre
Interval 1.0 to 1.0
|
300 Colony forming units per millilitre
Interval 50.0 to 10000.0
|
175 Colony forming units per millilitre
Interval 100.0 to 1000.0
|
SECONDARY outcome
Timeframe: From inoculation (day 0) to the final visit for each participant (28 days post-inoculation)Population: Proportion of participants with experimental colonisation who remain positive at A) day 13 post-prime inoculation, B) day 28 post-prime inoculation and C) day 14 post-targeted booster inoculation. Note, for row (C) the number of participants analyzed includes only those who developed experimental colonisation after booster inoculation (negative before that).
The duration of experimental SPN3 colonisation of nasopharynx determined by the last NW sample following one or two inoculations in which SPN3 is detected by classical microbiological culture, assessed for each isolate and dose separately. Note - number of participants analyzed in this outcome measure is different (and lower) than overall number of participants in participant flow section, because duration of colonisation can only apply to participants who developed experimental colonisation from at least one timepoint post-inoculation.
Outcome measures
| Measure |
MLW-10V, 10000 CFU/ml
n=5 Participants
Malawi isolate, low dose
|
MLW-10V, 20000 CFU/ml
n=2 Participants
Malawi isolate, intermediate dose
|
MLW-10V, 80000 CFU/ml
n=8 Participants
Malawi isolate, higher dose
|
LIV014-S3, 10000 CFU/ml
n=1 Participants
Liverpool isolate, low dose
|
LIV014-S3, 20000 CFU/ml
n=8 Participants
Liverpool isolate, intermediate dose
|
LIV014-S3, 80000 CFU/ml
n=34 Participants
Liverpool isolate, higher dose (includes dose-ranging and reproducibility study participants, since the reproducibility study only included this isolate and dose)
|
|---|---|---|---|---|---|---|
|
To Determine the Duration of Experimental SPN3 Colonisation of the Nasopharynx.
Participants with ongoing experimental colonisation at day 13 post-prime inoculation
|
4 Participants
|
0 Participants
|
5 Participants
|
0 Participants
|
4 Participants
|
19 Participants
|
|
To Determine the Duration of Experimental SPN3 Colonisation of the Nasopharynx.
Participants with ongoing experimental colonisation at day 28 post-prime inoculation
|
3 Participants
|
0 Participants
|
5 Participants
|
0 Participants
|
4 Participants
|
19 Participants
|
|
To Determine the Duration of Experimental SPN3 Colonisation of the Nasopharynx.
Participants with ongoing experimental colonisation at day 14 post-targeted booster inoculation
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
3 Participants
|
6 Participants
|
Adverse Events
MLW-10V, 10000 CFU/ml
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
MLW-10V, 20000 CFU/ml
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
MLW-10V, 80000 CFU/ml
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
LIV014-S3, 10000 CFU/ml
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
LIV014-S3, 20000 CFU/ml
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
LIV014-S3, 80000 CFU/ml
Serious events: 0 serious events
Other events: 28 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
MLW-10V, 10000 CFU/ml
n=9 participants at risk
Malawi isolate, low dose
|
MLW-10V, 20000 CFU/ml
n=10 participants at risk
Malawi isolate, intermediate dose
|
MLW-10V, 80000 CFU/ml
n=10 participants at risk
Malawi isolate, higher dose
|
LIV014-S3, 10000 CFU/ml
n=7 participants at risk
Liverpool isolate, low dose
|
LIV014-S3, 20000 CFU/ml
n=10 participants at risk
Liverpool isolate, intermediate dose
|
LIV014-S3, 80000 CFU/ml
n=40 participants at risk
Liverpool isolate, higher dose (includes dose-ranging and reproducibility study participants, since the reproducibility study only included this isolate and dose)
|
|---|---|---|---|---|---|---|
|
General disorders
Headache
|
0.00%
0/9 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
50.0%
5/10 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
10.0%
1/10 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
14.3%
1/7 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
20.0%
2/10 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
47.5%
19/40 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/9 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
30.0%
3/10 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
10.0%
1/10 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
28.6%
2/7 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
20.0%
2/10 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
10.0%
4/40 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
|
Ear and labyrinth disorders
Earache
|
0.00%
0/9 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
10.0%
1/10 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
10.0%
1/10 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
0.00%
0/7 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
10.0%
1/10 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
5.0%
2/40 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
|
Infections and infestations
Fever
|
0.00%
0/9 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
20.0%
2/10 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
0.00%
0/10 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
0.00%
0/7 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
0.00%
0/10 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
20.0%
8/40 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
|
Infections and infestations
Sore throat (pharyngitis)
|
11.1%
1/9 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
80.0%
8/10 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
40.0%
4/10 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
57.1%
4/7 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
50.0%
5/10 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
62.5%
25/40 • For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.
For non-serious adverse events, frequency is reported as total number for each arm; these adverse events are then subdivided into specific adverse events, for each arm.
|
Additional Information
Dr Andrea Collins ( Chief Investigator)
Liverpool School of Tropical Medicine
Phone: 0151 702 9439
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place