Trial Outcomes & Findings for In Vitro Evaluation of a Novel Drug on Airway Epithelial Cells Obtained From Participants With Severe Asthma (NCT NCT02740049)
NCT ID: NCT02740049
Last Updated: 2019-10-28
Results Overview
Measurement of cytokine levels in cell supernatant after stimulation of isolated epithelial cells. For this study epithelial cells from severe asthma patients (n = 9) were cultured and stimulated with either IFN/TNF or IL-13 to induce inflammation. Cells are then treated with VR588 (2 concentration) or with Fluticasone Propionate (FP) or with CP690553 (CP; Tofacitinib). The concentrations of drugs are listed in the title (e.g. 10-9M).
Recruitment status
COMPLETED
Study phase
EARLY_PHASE1
Target enrollment
9 participants
Primary outcome timeframe
21 days
Results posted on
2019-10-28
Participant Flow
Participant diagnosed with severe asthma were recruited from clinics at the Royal Brompton hospital between January 2016 and September 2016.
Participant milestones
| Measure |
Astma Patients
Participant undergoes a bronchoscopy to isolate epithelial cells
VR588: Evaluation of the efficacy of a novel JAK/STAT inhibitor, VR588, in isolated epithelial cells from asthma patients
|
|---|---|
|
Overall Study
STARTED
|
9
|
|
Overall Study
COMPLETED
|
8
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Astma Patients
Participant undergoes a bronchoscopy to isolate epithelial cells
VR588: Evaluation of the efficacy of a novel JAK/STAT inhibitor, VR588, in isolated epithelial cells from asthma patients
|
|---|---|
|
Overall Study
Isolated cells did not grow sufficiently
|
1
|
Baseline Characteristics
In Vitro Evaluation of a Novel Drug on Airway Epithelial Cells Obtained From Participants With Severe Asthma
Baseline characteristics by cohort
| Measure |
Astma Patients
n=9 Participants
Participant undergoes a bronchoscopy to isolate epithelial cells
VR588: Evaluation of the efficacy of a novel JAK/STAT inhibitor, VR588, in isolated epithelial cells from asthma patients
|
|---|---|
|
Age, Customized
Participants
|
51.9 years
STANDARD_DEVIATION 15.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Indian
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
8 Participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
9 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 21 daysPopulation: 1 participant's cell did not grow
Measurement of cytokine levels in cell supernatant after stimulation of isolated epithelial cells. For this study epithelial cells from severe asthma patients (n = 9) were cultured and stimulated with either IFN/TNF or IL-13 to induce inflammation. Cells are then treated with VR588 (2 concentration) or with Fluticasone Propionate (FP) or with CP690553 (CP; Tofacitinib). The concentrations of drugs are listed in the title (e.g. 10-9M).
Outcome measures
| Measure |
Astma Patients
n=8 Participants
Participant undergoes a bronchoscopy to isolate epithelial cells
VR588: Evaluation of the efficacy of a novel JAK/STAT inhibitor, VR588, in isolated epithelial cells from asthma patients
|
|---|---|
|
Concentration (pg/ml) of CXCL8 Cytokine in Cell Supernatant After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
Non-treated Control
|
2090.0 pg/ml
Standard Deviation 319.7
|
|
Concentration (pg/ml) of CXCL8 Cytokine in Cell Supernatant After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
Non-treated VR588 10-8M
|
1835.2 pg/ml
Standard Deviation 818.1
|
|
Concentration (pg/ml) of CXCL8 Cytokine in Cell Supernatant After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
Non-treated VR588 10-7M
|
1863.7 pg/ml
Standard Deviation 310.9
|
|
Concentration (pg/ml) of CXCL8 Cytokine in Cell Supernatant After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
Non-treated CP 10-7M
|
1815.1 pg/ml
Standard Deviation 605.1
|
|
Concentration (pg/ml) of CXCL8 Cytokine in Cell Supernatant After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
Non-treated FP 10-8M
|
1635.1 pg/ml
Standard Deviation 530.1
|
|
Concentration (pg/ml) of CXCL8 Cytokine in Cell Supernatant After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IFN/TNF
|
7000.5 pg/ml
Standard Deviation 1047.4
|
|
Concentration (pg/ml) of CXCL8 Cytokine in Cell Supernatant After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IFN/TNF VR588 10-9M
|
5402.1 pg/ml
Standard Deviation 1427.5
|
|
Concentration (pg/ml) of CXCL8 Cytokine in Cell Supernatant After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IFN/TNF VR588 10-7M
|
3996.4 pg/ml
Standard Deviation 988.5
|
|
Concentration (pg/ml) of CXCL8 Cytokine in Cell Supernatant After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IFN/TNF CP 10-7M
|
3050.4 pg/ml
Standard Deviation 924.1
|
|
Concentration (pg/ml) of CXCL8 Cytokine in Cell Supernatant After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IFN/TNF FP 10-8M
|
2558.6 pg/ml
Standard Deviation 895.5
|
|
Concentration (pg/ml) of CXCL8 Cytokine in Cell Supernatant After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IL-13
|
8686.3 pg/ml
Standard Deviation 2024.3
|
|
Concentration (pg/ml) of CXCL8 Cytokine in Cell Supernatant After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IL-13 VR588 10-9M
|
6188.6 pg/ml
Standard Deviation 734.3
|
|
Concentration (pg/ml) of CXCL8 Cytokine in Cell Supernatant After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IL-13 VR588 10-7M
|
4555.2 pg/ml
Standard Deviation 1467.9
|
|
Concentration (pg/ml) of CXCL8 Cytokine in Cell Supernatant After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IL-13 CP 10-7M
|
4599.8 pg/ml
Standard Deviation 1649.7
|
|
Concentration (pg/ml) of CXCL8 Cytokine in Cell Supernatant After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IL-13 FP 10-8M
|
4639.0 pg/ml
Standard Deviation 905.9
|
PRIMARY outcome
Timeframe: 21 daysPopulation: 1 participant's cell did not grow
Measurement of cell viability after stimulation of isolated epithelial cells. For this study epithelial cells from severe asthma patients (n = 9) were cultured and stimulated with either IFN/TNF or IL-13 to induce inflammation. Cells are then treated with VR588 (2 concentration) or with Fluticasone Propionate (FP) or with CP690553 (CP; Tofacitinib). The concentrations of drugs are listed in the title (e.g. 10-9M).
Outcome measures
| Measure |
Astma Patients
n=8 Participants
Participant undergoes a bronchoscopy to isolate epithelial cells
VR588: Evaluation of the efficacy of a novel JAK/STAT inhibitor, VR588, in isolated epithelial cells from asthma patients
|
|---|---|
|
Percentage of Viable Cells Compared to Baseline After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
Non-treated Control
|
100.0 percentage against baseline
Standard Deviation 30.1
|
|
Percentage of Viable Cells Compared to Baseline After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
Non-treated VR588 10-9M
|
98.4 percentage against baseline
Standard Deviation 23.1
|
|
Percentage of Viable Cells Compared to Baseline After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
Non-treated VR588 10-7M
|
95.4 percentage against baseline
Standard Deviation 23.2
|
|
Percentage of Viable Cells Compared to Baseline After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
Non-treated CP 10-7M
|
98.4 percentage against baseline
Standard Deviation 14.1
|
|
Percentage of Viable Cells Compared to Baseline After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
Non-treated FP 10-8M
|
102.9 percentage against baseline
Standard Deviation 27.1
|
|
Percentage of Viable Cells Compared to Baseline After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IFN/TNF
|
87.1 percentage against baseline
Standard Deviation 10.5
|
|
Percentage of Viable Cells Compared to Baseline After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IFN/TNF VR588 10-9M
|
92.0 percentage against baseline
Standard Deviation 15.0
|
|
Percentage of Viable Cells Compared to Baseline After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IFN/TNF VR588 10-7M
|
93.3 percentage against baseline
Standard Deviation 14.5
|
|
Percentage of Viable Cells Compared to Baseline After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IFN/TNF CP 10-7M
|
96.6 percentage against baseline
Standard Deviation 10.5
|
|
Percentage of Viable Cells Compared to Baseline After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IFN/TNF FP 10-8M
|
82.2 percentage against baseline
Standard Deviation 11.2
|
|
Percentage of Viable Cells Compared to Baseline After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IL-13
|
91.4 percentage against baseline
Standard Deviation 12.4
|
|
Percentage of Viable Cells Compared to Baseline After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IL-13 VR588 10-9M
|
86.9 percentage against baseline
Standard Deviation 14.2
|
|
Percentage of Viable Cells Compared to Baseline After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IL-13 VR588 10-7M
|
90.0 percentage against baseline
Standard Deviation 10.7
|
|
Percentage of Viable Cells Compared to Baseline After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IL-13 CP 10-7M
|
89.0 percentage against baseline
Standard Deviation 11.7
|
|
Percentage of Viable Cells Compared to Baseline After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IL-13 FP 10-8M
|
92.7 percentage against baseline
Standard Deviation 12.4
|
PRIMARY outcome
Timeframe: 21 daysPopulation: 1 participant's cell did not grow
Measurement of activation of phospho-STAT1 member of the JAK/STAT signaltransduction pathway in cell lysates. For this study epithelial cells from severe asthma patients (n = 9) were cultured and stimulated with either IFN/TNF or IL-13 to induce inflammation. Cells are then treated with VR588 (2 concentration) or with Fluticasone Propionate (FP) or with CP690553 (CP; Tofacitinib). The concentrations of drugs are listed in the title (e.g. 10-9M).
Outcome measures
| Measure |
Astma Patients
n=8 Participants
Participant undergoes a bronchoscopy to isolate epithelial cells
VR588: Evaluation of the efficacy of a novel JAK/STAT inhibitor, VR588, in isolated epithelial cells from asthma patients
|
|---|---|
|
Relative Fluorescence Units of STAT1 Protein Phosphorylation After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IL-13 VR588 10-9M
|
1.97 Relative Fluorescence Units
Standard Deviation 1.37
|
|
Relative Fluorescence Units of STAT1 Protein Phosphorylation After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
Non-treated Control
|
0.80 Relative Fluorescence Units
Standard Deviation 0.11
|
|
Relative Fluorescence Units of STAT1 Protein Phosphorylation After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
Non-treated VR588 10-9M
|
0.82 Relative Fluorescence Units
Standard Deviation 0.13
|
|
Relative Fluorescence Units of STAT1 Protein Phosphorylation After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
Non-treated VR588 10-7M
|
0.74 Relative Fluorescence Units
Standard Deviation 0.20
|
|
Relative Fluorescence Units of STAT1 Protein Phosphorylation After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
Non-treated CP 10-7M
|
0.64 Relative Fluorescence Units
Standard Deviation 0.22
|
|
Relative Fluorescence Units of STAT1 Protein Phosphorylation After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
Non-treated FP 10-8M
|
0.60 Relative Fluorescence Units
Standard Deviation 0.28
|
|
Relative Fluorescence Units of STAT1 Protein Phosphorylation After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IFN/TNF
|
6.94 Relative Fluorescence Units
Standard Deviation 1.75
|
|
Relative Fluorescence Units of STAT1 Protein Phosphorylation After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IFN/TNF VR588 10-9M
|
4.99 Relative Fluorescence Units
Standard Deviation 1.82
|
|
Relative Fluorescence Units of STAT1 Protein Phosphorylation After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IFN/TNF VR588 10-7M
|
4.15 Relative Fluorescence Units
Standard Deviation 1.55
|
|
Relative Fluorescence Units of STAT1 Protein Phosphorylation After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IFN/TNF CP 10-7M
|
1.56 Relative Fluorescence Units
Standard Deviation 0.96
|
|
Relative Fluorescence Units of STAT1 Protein Phosphorylation After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IFN/TNF FP 10-8M
|
3.20 Relative Fluorescence Units
Standard Deviation 1.36
|
|
Relative Fluorescence Units of STAT1 Protein Phosphorylation After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IL-13
|
4.24 Relative Fluorescence Units
Standard Deviation 1.72
|
|
Relative Fluorescence Units of STAT1 Protein Phosphorylation After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IL-13 VR588 10-7M
|
1.38 Relative Fluorescence Units
Standard Deviation 0.71
|
|
Relative Fluorescence Units of STAT1 Protein Phosphorylation After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IL-13 CP 10-7M
|
0.89 Relative Fluorescence Units
Standard Deviation 0.36
|
|
Relative Fluorescence Units of STAT1 Protein Phosphorylation After Stimulation (IFN/TNF or IL13) and Treatment (VR588, FP or CP) Conditions in ALI Cultured Epithelial Cells.
IL-13 FP 10-8M
|
0.96 Relative Fluorescence Units
Standard Deviation 0.37
|
Adverse Events
Astma Patients
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
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place