Trial Outcomes & Findings for Identification of Autoantigens in EGPA and Severe Eosinophilic Asthma (NCT NCT04671446)

NCT ID: NCT04671446

Last Updated: 2025-01-30

Results Overview

Serum tested for novel autoantibodies against candidate auto-antigens by ELISA. Outcome: Positive OD by ELISA (serum samples) to autoantigen panel (MPO, Collagen V, TREM1, IL1R2).

Recruitment status

COMPLETED

Target enrollment

120 participants

Primary outcome timeframe

Baseline, at study entry

Results posted on

2025-01-30

Participant Flow

Participant milestones

Participant milestones
Measure
Severe Eosinophilic Asthma
Patients with eosinophilic asthma meeting ERS/ATS criteria for severe asthma.
Healthy Controls
Healthy patients with no chronic lung condition.
EGPA
Patients with asthma meeting criteria for a diagnosis of EGPA (eosinophilic granulomatosis with polyangiitis)
Other Respiratory Conditions
Mild-to-moderate asthma, other vasculitides, eosinophilic COPD, and/or eosinophilic oesophagitis
Overall Study
STARTED
63
30
17
10
Overall Study
COMPLETED
63
30
17
10
Overall Study
NOT COMPLETED
0
0
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Age for one healthy control not available.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Severe Eosinophilic Asthma
n=63 Participants
Patients with eosinophilic asthma meeting ERS/ATS criteria for severe asthma.
Healthy Controls
n=30 Participants
Healthy patients with no chronic lung condition.
EGPA
n=17 Participants
Patients with asthma meeting criteria for a diagnosis of EGPA (eosinophilic granulomatosis with polyangiitis)
Other Respiratory Conditions
n=10 Participants
Mild-to-moderate asthma, other vasculitides, eosinophilic COPD, and/or eosinophilic oesophagitis
Total
n=120 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=63 Participants • Age for one healthy control not available.
0 Participants
n=29 Participants • Age for one healthy control not available.
0 Participants
n=17 Participants • Age for one healthy control not available.
0 Participants
n=10 Participants • Age for one healthy control not available.
0 Participants
n=119 Participants • Age for one healthy control not available.
Age, Categorical
Between 18 and 65 years
54 Participants
n=63 Participants • Age for one healthy control not available.
28 Participants
n=29 Participants • Age for one healthy control not available.
13 Participants
n=17 Participants • Age for one healthy control not available.
5 Participants
n=10 Participants • Age for one healthy control not available.
100 Participants
n=119 Participants • Age for one healthy control not available.
Age, Categorical
>=65 years
9 Participants
n=63 Participants • Age for one healthy control not available.
1 Participants
n=29 Participants • Age for one healthy control not available.
4 Participants
n=17 Participants • Age for one healthy control not available.
5 Participants
n=10 Participants • Age for one healthy control not available.
19 Participants
n=119 Participants • Age for one healthy control not available.
Age, Continuous
54.4 years
STANDARD_DEVIATION 12.3 • n=63 Participants • Age for one Healthy control patient not available
42.0 years
STANDARD_DEVIATION 14.1 • n=29 Participants • Age for one Healthy control patient not available
56.6 years
STANDARD_DEVIATION 14.2 • n=17 Participants • Age for one Healthy control patient not available
63.1 years
STANDARD_DEVIATION 9.7 • n=10 Participants • Age for one Healthy control patient not available
52.4 years
STANDARD_DEVIATION 14.2 • n=119 Participants • Age for one Healthy control patient not available
Sex: Female, Male
Female
29 Participants
n=63 Participants
16 Participants
n=30 Participants
7 Participants
n=17 Participants
4 Participants
n=10 Participants
56 Participants
n=120 Participants
Sex: Female, Male
Male
34 Participants
n=63 Participants
14 Participants
n=30 Participants
10 Participants
n=17 Participants
6 Participants
n=10 Participants
64 Participants
n=120 Participants
Race/Ethnicity, Customized
Ethnicity · White
31 Participants
n=63 Participants
16 Participants
n=30 Participants
12 Participants
n=17 Participants
6 Participants
n=10 Participants
65 Participants
n=120 Participants
Race/Ethnicity, Customized
Ethnicity · Asian
16 Participants
n=63 Participants
9 Participants
n=30 Participants
0 Participants
n=17 Participants
4 Participants
n=10 Participants
29 Participants
n=120 Participants
Race/Ethnicity, Customized
Ethnicity · Black
8 Participants
n=63 Participants
0 Participants
n=30 Participants
2 Participants
n=17 Participants
0 Participants
n=10 Participants
10 Participants
n=120 Participants
Race/Ethnicity, Customized
Ethnicity · Other / Declined / Not Available
8 Participants
n=63 Participants
5 Participants
n=30 Participants
3 Participants
n=17 Participants
0 Participants
n=10 Participants
16 Participants
n=120 Participants
Region of Enrollment
United Kingdom
63 participants
n=63 Participants
30 participants
n=30 Participants
17 participants
n=17 Participants
10 participants
n=10 Participants
120 participants
n=120 Participants

PRIMARY outcome

Timeframe: Baseline, at study entry

Population: EGPA and Other respiratory conditions arms included as reference populations, with some patients purposefully recruited due to known anti-MPO status (potential selection bias). 17 Severe eosinophilic asthma patients, 5 Healthy control participants, 5 EGPA patients and 3 patients with Other Respiratory Conditions excluded from outcome due to technical errors with ELISA assays (missing data).

Serum tested for novel autoantibodies against candidate auto-antigens by ELISA. Outcome: Positive OD by ELISA (serum samples) to autoantigen panel (MPO, Collagen V, TREM1, IL1R2).

Outcome measures

Outcome measures
Measure
Severe Eosinophilic Asthma
n=46 Participants
Patients with eosinophilic asthma meeting ERS/ATS criteria for severe asthma.
Healthy Controls
n=25 Participants
Healthy patients with no chronic lung condition.
EGPA
n=12 Participants
Patients with asthma meeting criteria for a diagnosis of EGPA (eosinophilic granulomatosis with polyangiitis)
Other Respiratory Conditions
n=7 Participants
Mild-to-moderate asthma, other vasculitides, eosinophilic COPD, and/or eosinophilic oesophagitis
Number and Percentage of Patients With a Positive Autoantibody ELISA
19 Participants
4 Participants
3 Participants
4 Participants

SECONDARY outcome

Timeframe: Baseline, at study entry

Population: EGPA and Other respiratory conditions arms included as reference populations, with some patients purposefully recruited due to known anti-MPO status (potential selection bias). 46 Severe eosinophilic asthma patients, 23 Healthy control participants, 12 EGPA patients and 10 patients with Other Respiratory Conditions excluded from outcome due to missing data (only limited samples were tested).

FITC anti-IgG immunofluorescence with slides of unstimulated/PMA-stimulated neutrophils (serum samples)

Outcome measures

Outcome measures
Measure
Severe Eosinophilic Asthma
n=17 Participants
Patients with eosinophilic asthma meeting ERS/ATS criteria for severe asthma.
Healthy Controls
n=7 Participants
Healthy patients with no chronic lung condition.
EGPA
n=5 Participants
Patients with asthma meeting criteria for a diagnosis of EGPA (eosinophilic granulomatosis with polyangiitis)
Other Respiratory Conditions
Mild-to-moderate asthma, other vasculitides, eosinophilic COPD, and/or eosinophilic oesophagitis
Number and Percentage of Patients With Positive Granulocyte Immunofluorescence
9 Participants
1 Participants
3 Participants

POST_HOC outcome

Timeframe: Baseline, at study entry

Population: Peripheral blood samples for sequencing were only available for a proportion of participants. 60 participants were chosen for this post-hoc analysis to represent a range of SEA/EGPA patients and healthy controls. Sequencing from 1 sample did not reach quality control criteria resulting in 59 samples reported. No participants with Other respiratory conditions were analysed for this post-hoc outcome as these were not the population of interest for this post-hoc outcome measure.

Peripheral blood B Cell Receptor (BCR) bulkRNA repertoire sequencing

Outcome measures

Outcome measures
Measure
Severe Eosinophilic Asthma
n=31 Participants
Patients with eosinophilic asthma meeting ERS/ATS criteria for severe asthma.
Healthy Controls
n=16 Participants
Healthy patients with no chronic lung condition.
EGPA
n=12 Participants
Patients with asthma meeting criteria for a diagnosis of EGPA (eosinophilic granulomatosis with polyangiitis)
Other Respiratory Conditions
Mild-to-moderate asthma, other vasculitides, eosinophilic COPD, and/or eosinophilic oesophagitis
Percentage of Total Unique BCR Sequences Being of IgA1 Subclass
0.89 Percentage of unique BCR sequences
Standard Deviation 0.58
0.82 Percentage of unique BCR sequences
Standard Deviation 0.48
1.68 Percentage of unique BCR sequences
Standard Deviation 1.07

POST_HOC outcome

Timeframe: Baseline, at study entry

Population: Peripheral blood samples for sequencing were only available for a proportion of participants. 60 participants were chosen for this post-hoc analysis to represent a range of SEA/EGPA patients and healthy controls. Sequencing from 1 sample did not reach quality control criteria resulting in 59 samples reported. No participants with Other respiratory conditions were analysed for this post-hoc outcome as these were not the population of interest for this post-hoc outcome measure.

Peripheral blood B Cell Receptor (BCR) bulkRNA repertoire sequencing

Outcome measures

Outcome measures
Measure
Severe Eosinophilic Asthma
n=31 Participants
Patients with eosinophilic asthma meeting ERS/ATS criteria for severe asthma.
Healthy Controls
n=16 Participants
Healthy patients with no chronic lung condition.
EGPA
n=12 Participants
Patients with asthma meeting criteria for a diagnosis of EGPA (eosinophilic granulomatosis with polyangiitis)
Other Respiratory Conditions
Mild-to-moderate asthma, other vasculitides, eosinophilic COPD, and/or eosinophilic oesophagitis
Percentage of Total Unique BCR Sequences Being of IgA2 Subclass
1.33 Percentage of unique BCR sequences
Standard Deviation 1.18
0.85 Percentage of unique BCR sequences
Standard Deviation 0.48
1.59 Percentage of unique BCR sequences
Standard Deviation 1.23

POST_HOC outcome

Timeframe: Baseline, at study entry

Population: Peripheral blood samples for sequencing were only available for a proportion of participants. 60 participants were chosen for this post-hoc analysis to represent a range of SEA/EGPA patients and healthy controls. Sequencing from 1 sample did not reach quality control criteria resulting in 59 samples reported. No participants with Other respiratory conditions were analysed for this post-hoc outcome as these were not the population of interest for this post-hoc outcome measure.

Peripheral blood B Cell Receptor (BCR) bulkRNA repertoire sequencing

Outcome measures

Outcome measures
Measure
Severe Eosinophilic Asthma
n=31 Participants
Patients with eosinophilic asthma meeting ERS/ATS criteria for severe asthma.
Healthy Controls
n=16 Participants
Healthy patients with no chronic lung condition.
EGPA
n=12 Participants
Patients with asthma meeting criteria for a diagnosis of EGPA (eosinophilic granulomatosis with polyangiitis)
Other Respiratory Conditions
Mild-to-moderate asthma, other vasculitides, eosinophilic COPD, and/or eosinophilic oesophagitis
Percentage of Total Unique BCR Sequences Being of IgG1 Subclass
2.52 Percentage of unique BCR sequences
Standard Deviation 2.18
2.05 Percentage of unique BCR sequences
Standard Deviation 1.36
2.90 Percentage of unique BCR sequences
Standard Deviation 1.34

POST_HOC outcome

Timeframe: Baseline, at study entry

Population: Peripheral blood samples for sequencing were only available for a proportion of participants. 60 participants were chosen for this post-hoc analysis to represent a range of SEA/EGPA patients and healthy controls. Sequencing from 1 sample did not reach quality control criteria resulting in 59 samples reported. No participants with Other respiratory conditions were analysed for this post-hoc outcome as these were not the population of interest for this post-hoc outcome measure.

Peripheral blood B Cell Receptor (BCR) bulkRNA repertoire sequencing

Outcome measures

Outcome measures
Measure
Severe Eosinophilic Asthma
n=31 Participants
Patients with eosinophilic asthma meeting ERS/ATS criteria for severe asthma.
Healthy Controls
n=16 Participants
Healthy patients with no chronic lung condition.
EGPA
n=12 Participants
Patients with asthma meeting criteria for a diagnosis of EGPA (eosinophilic granulomatosis with polyangiitis)
Other Respiratory Conditions
Mild-to-moderate asthma, other vasculitides, eosinophilic COPD, and/or eosinophilic oesophagitis
Percentage of Total Unique BCR Sequences Being of IgG2 Subclass
7.86 Percentage of unique BCR sequences
Standard Deviation 9.46
3.15 Percentage of unique BCR sequences
Standard Deviation 1.50
8.37 Percentage of unique BCR sequences
Standard Deviation 9.20

POST_HOC outcome

Timeframe: Baseline, at study entry

Population: Peripheral blood samples for sequencing were only available for a proportion of participants. 60 participants were chosen for this post-hoc analysis to represent a range of SEA/EGPA patients and healthy controls. Sequencing from 1 sample did not reach quality control criteria resulting in 59 samples reported. No participants with Other respiratory conditions were analysed for this post-hoc outcome as these were not the population of interest for this post-hoc outcome measure.

Peripheral blood B Cell Receptor (BCR) bulkRNA repertoire sequencing

Outcome measures

Outcome measures
Measure
Severe Eosinophilic Asthma
n=31 Participants
Patients with eosinophilic asthma meeting ERS/ATS criteria for severe asthma.
Healthy Controls
n=16 Participants
Healthy patients with no chronic lung condition.
EGPA
n=12 Participants
Patients with asthma meeting criteria for a diagnosis of EGPA (eosinophilic granulomatosis with polyangiitis)
Other Respiratory Conditions
Mild-to-moderate asthma, other vasculitides, eosinophilic COPD, and/or eosinophilic oesophagitis
Percentage of Total Unique BCR Sequences Being of IgG3 Subclass
0.60 Percentage of unique BCR sequences
Standard Deviation 0.55
0.69 Percentage of unique BCR sequences
Standard Deviation 0.79
0.68 Percentage of unique BCR sequences
Standard Deviation 0.58

POST_HOC outcome

Timeframe: Baseline, at study entry

Population: Peripheral blood samples for sequencing were only available for a proportion of participants. 60 participants were chosen for this post-hoc analysis to represent a range of SEA/EGPA patients and healthy controls. Sequencing from 1 sample did not reach quality control criteria resulting in 59 samples reported. No participants with Other respiratory conditions were analysed for this post-hoc outcome as these were not the population of interest for this post-hoc outcome measure.

Peripheral blood B Cell Receptor (BCR) bulkRNA repertoire sequencing

Outcome measures

Outcome measures
Measure
Severe Eosinophilic Asthma
n=31 Participants
Patients with eosinophilic asthma meeting ERS/ATS criteria for severe asthma.
Healthy Controls
n=16 Participants
Healthy patients with no chronic lung condition.
EGPA
n=12 Participants
Patients with asthma meeting criteria for a diagnosis of EGPA (eosinophilic granulomatosis with polyangiitis)
Other Respiratory Conditions
Mild-to-moderate asthma, other vasculitides, eosinophilic COPD, and/or eosinophilic oesophagitis
Percentage of Total Unique BCR Sequences Being of IgG4 Subclass
0.059 Percentage of unique BCR sequences
Standard Deviation 0.10
0.011 Percentage of unique BCR sequences
Standard Deviation 0.0086
0.051 Percentage of unique BCR sequences
Standard Deviation 0.048

POST_HOC outcome

Timeframe: Baseline, at study entry

Population: Peripheral blood samples for sequencing were only available for a proportion of participants. 60 participants were chosen for this post-hoc analysis to represent a range of SEA/EGPA patients and healthy controls. Sequencing from 1 sample did not reach quality control criteria resulting in 59 samples reported. No participants with Other respiratory conditions were analysed for this post-hoc outcome as these were not the population of interest for this post-hoc outcome measure.

Peripheral blood B Cell Receptor (BCR) bulkRNA repertoire sequencing

Outcome measures

Outcome measures
Measure
Severe Eosinophilic Asthma
n=31 Participants
Patients with eosinophilic asthma meeting ERS/ATS criteria for severe asthma.
Healthy Controls
n=16 Participants
Healthy patients with no chronic lung condition.
EGPA
n=12 Participants
Patients with asthma meeting criteria for a diagnosis of EGPA (eosinophilic granulomatosis with polyangiitis)
Other Respiratory Conditions
Mild-to-moderate asthma, other vasculitides, eosinophilic COPD, and/or eosinophilic oesophagitis
Percentage of Total Unique BCR Sequences Being of IgE Subclass
0.017 Percentage of unique BCR sequences
Standard Deviation 0.012
0.0060 Percentage of unique BCR sequences
Standard Deviation 0.0029
0.039 Percentage of unique BCR sequences
Standard Deviation 0.040

Adverse Events

Severe Eosinophilic Asthma

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Healthy Controls

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

EGPA

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Other Respiratory Conditions

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr Myles Lewis, Dr Paul Pfeffer

Queen Mary University of London

Phone: +4420 7882 5555

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place