Asthma
Conditions
Keywords
cKIT inhibition in Asthma, Efficacy of Imatinib in severe resistent asthma.
Brief summary
The purpose of this study is to see whether a new investigational drug (Imatinib) may help improve asthma in people whose symptoms are not well controlled with high dose inhaled corticosteroid treatment.
Detailed description
Severe asthmatics remain poorly controlled despite high doses of standard asthma therapy or even daily doses of systemic corticosteroids or their equivalent. They account for a large proportion of the morbidity and mortality associated with asthma. Features that seem to characterize many patients with this disorder include persistent inflammation, symptoms, and airway hyperresponsiveness in the face of corticosteroid therapy. Mast cells are powerful, long-lived tissue dwelling effector cells that are resistant to corticosteroid effects and have been implicated in the pathobiology of asthma. Mast cells in the airway smooth muscle have been found to be the major distinguishing difference between asthmatic and non-asthmatic eosinophil airway disease; and putative circulating mast cell progenitors are increased 5 fold in asthma. Stem cell factor (SCF) is critical to mast cell homeostasis and upregulation and has pleiotropic effects on mast cells and eosinophils . SCF levels are elevated in relation to asthma severity and SCF antibodies block hyperresponsiveness and inflammation and remodeling in murine asthma models. Imatinib, a specific tyrosine kinase inhibitor, inhibits cKit (Kit), the receptor for SCF on mast cells. Imatinib at doses equivalent to, or below, doses safely used in humans, also mimics or exceeds anti-SCF effects in the murine asthma model. Therefore we would like to know Does imatinib, an inhibitor of Kit, ameliorate severe asthma, in association with effects on lung mast cell phenotype and/or function? Specific Aims of the study are: Specific Aim 1: To investigate whether, in patients with persistent airway responsiveness and poor asthma control despite intensive asthma therapy, 24 weeks of imatinib therapy results in a reduction in airway responsiveness and in secondary indicators of asthma control, airway inflammation, and structural changes in the airways. Patients will be treated with imatinib in a randomized, double-blind, placebo controlled trial. Assessments will include methacholine and AMP reactivity, airway function, symptoms, airway wall thickness by CT scan, analysis of induced sputum, non-invasive markers of airway inflammation, and bronchoscopy including endobronchial biopsy and bronchoalveolar lavage - all before and at the end of therapy. Specific Aim 2: To investigate whether, in patients with persistent airway responsiveness and poor asthma control despite intensive asthma therapy, 24 weeks of imatinib therapy results in changes in airway mast cell population and/or phenotype.
Interventions
DRUGImatinib mesylate
Imatinib will be initiated at an oral dose of 200 mg (two 100 mg film-coated tables) per day during the first two weeks of treatment. If the treatment is well tolerated, an up-titration to 400 mg daily (four 100 mg film-coated tables) will occur.
DRUGPlacebo
Placebo
Sponsors
Baim Institute for Clinical Research
National Heart, Lung, and Blood Institute (NHLBI)
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Patients 18-65 years of age, diagnosed with asthma for at least 1 year; 2. Refractory asthma, defined as reporting that their asthma has not been completely controlled in the past 3 months despite continuous treatment with high-dose inhaled corticosteroids (ICS) and an additional controller medication, with or without continuous oral corticosteroids (OCS)
Exclusion criteria
1. Current smoking or smoking history of greater than 10 pack-years 2. Any other significant respiratory or cardiac disease, or the presence of clinically important comorbidities, including uncontrolled diabetes, uncontrolled coronary artery disease 3. If subject cannot undergo bronchoscopy procedure due to safety reasons 4. Previous treatment with Imatinib 5. A history of acute heart failure or chronic left sided heart failure 6. Uncontrolled systemic arterial hypertension 7. History of major bleeding or intracranial hemorrhage 8. History of immunodeficiency diseases, including HIV 9. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer 10. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. 11. Diagnosis of Hepatitis B or C. 12. History of alcohol abuse within 6 months of screening. 13. History of illicit drug abuse within 6 months of screening. 14. Regular use of anticoagulants (eg: Warfarin Sodium, Coumadin), amiodarone, carbamazepine, Cyclosporine, Rifampicin, or reverse transcriptase inhibitors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Methacholine Responsiveness as Assessed by the Provocation Concentration Causing a 20% Fall in Forced Expiratory Volume in One Second (FEV1) (PC20) at Month 3 and 6 Versus Baseline | Over 6 months from beginning of treatment | Our primary outcome was change in airway hyperresponsiveness, as assessed by PC20, from baseline to 3 and/or 6 months of therapy in imatinib treated participants as compared with controls. Change in PC20 was assessed using log2-transformed ratios of PC20 at month 3 and /or month 6 vs PC20 at baseline. Our null hypothesis was that the mean of this ratio will be 0 after log2-transformed. We used a linear mixed-effects model for a repeated-measures analysis to compare the primary outcome between the two groups. PC20 is determined by the provocation concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Airway Wall Thickness | 6 months after start of treatment | Change in airway wall thickness as assessed by computerized tomography (CT) |
| Serum Total Tryptase | 6 months after start of treatment | Change in serum total tryptase after 24 weeks of imatinib vs placebo treatment |
| Bronchoalveolar Lavage (BAL) Fluid Tryptase Level | 6 months after start of treatment | Change in BAL fluid tryptase levels after 24 weeks of imatinib vs. placebo |
| Change in Maximum Post-Bronchodilator (BD) Forced Expiratory Volume in One Second (FEV1) % | 6 months after start of treatment | — |
| Number of Asthma Exacerbations | Up to 24 weeks | Number of asthma exacerbations experienced from randomization to study completion. |
| FEV1 in Liters | 6 months after start of treatment | Change in FEV1 in treatment group compared to placebo group |
| FEV1% | 6 months after start of treatment | Change in FEV1% of predicted |
| Morning Peak Flow Measurement | 6 months after start of treatment | Change in patient-reported morning peak flow measurement (L/s) |
| Evening Peak Flow | 6 months after start of treatment | Change in patient-reported evening peak flow measurement (L/s) |
| Fractional Exhaled Nitric Oxide (FeNO) | 6 months after start of treatment | Change in Fractional Exhaled Nitric Oxide Measurement (ppb) |
| Asthma Control Questionnaire (ACQ) | 6 months after start of treatment | Change in patient-reported ACQ score The six-item Asthma Control Questionnaire (ACQ-6) is a scale from 0 to 6 with a lower value denoting an improvement in asthma control. The minimal important difference is 0.5. |
| Asthma Quality of Life Questionnaire (AQLQ) | 6 months after start of treatment | Change in patient-reported Asthma Quality of Life Questionnaire (AQLQ) score The asthma quality of life questionnaire (AQLQ) is a 32-item scale with a range from 1-7 with a higher value denoting improvement. The minimal important difference is 0.5. |
| Asthma Symptom Utility Index (ASUI) | 6 months after start of treatment | Change in patient reported ASUI score The asthma symptom utility index (ASUI) is a 10-item weighted scale with a range from 0.2 to 1 with a higher value indicating improvement. The minimal important difference is 0.09. |
| Blood Eosinophils | 6 months after start of treatment | Change in blood eosinophil count |
| BAL Eosinophil % | 6 months after start of treatment | Change in BAL eosinophil percentage |
| Bronchoalveolar Lavage (BAL) PGD2 | 6 months after start of treatment | Change in bronchoalveolar lavage (BAL) PGD2 levels from baseline at 6 months |
| Endobronchial Biopsy Total Tryptase-positive Mast Cells | 6 months after start of treatment | Change in endobronchial biopsy total tryptase-positive mast cells from baseline at 6 months |
| Endobronchial Biopsy Smooth Muscle Tryptase-positive Mast Cells | 6 months after start of treatment | Change in the biopsy smooth muscle tryptase-positive mast cells from baseline at 6 months |
| Airway Wall Area | 6 months after start of treatment | Change in airway wall area as assessed by computerized tomography (CT) |
| Bronchoalveolar Lavage Histamine | 6 months after start of treatment | Change in bronchoalveolar lavage histamine levels from baseline |
| Urinary Prostaglandin D2 | 6 months after start of treatment | Change in urinary Prostaglandin D2 levels from baseline |
| Bronchoalveolar Lavage Cysteinyl Leukotrienes | 6 months after start of treatment | Change in bronchoalveolar lavage cysteinyl leukotrienes levels from baseline |
| Urinary Leukotriene E4 | 6 months after start of treatment | Change in urinary leukotriene E4 levels from baseline |
| Change in Sputum Supernatant Differential, Supernatant Tryptase and IL-13 | baseline to 24 weeks | Change in sputum eosinophil and neutrophil percentage. Change in sputum supernatant tryptase as measured by ELISA. Change in sputum IL-13 level as measured by ELISA. |
| Change in Inflammatory Mediators in Exhaled Breath Condensate | baseline to week 24 | Assessment of change in eicosanoids in the exhaled breath condensate |
| Change in Number of Self-Reported Asthma Symptom Free Days | baseline to week 24 | — |
| BAL Neutrophil % | 6 months after start of treatment | Change in BAL neutrophil percentage from baseline |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from November 2010 until December 2014 in seven academic medical centers.
Pre-assignment details
Following enrollment, 176 subjects entered a run-in period in which several inclusion criteria had to be met prior to randomization, including ACQ requirements and methacholine sensitivity, as well as safety and compliance requirements. 114 subjects who did not meet these inclusion criteria were not randomized.
Participants by arm
| Arm | Count |
|---|---|
| Imatinib Mesylate Group on active imatinib treatment
Imatinib mesylate: Imatinib will be initiated at an oral dose of 200 mg (two 100 mg film-coated tables) per day during the first two weeks of treatment. If the treatment is well tolerated, an up-titration to 400 mg daily (four 100 mg film-coated tables) will occur. | 32 |
| Placebo Group on Placebo treatment
Placebo: Placebo | 30 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 0 |
| Overall Study | Lost to Follow-up | 0 | 3 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Imatinib Mesylate | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 30 Participants | 62 Participants |
| Age, Continuous | 40.2 years STANDARD_DEVIATION 10.2 | 37.7 years STANDARD_DEVIATION 11.8 | 40.1 years STANDARD_DEVIATION 11.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 5 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 25 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 13 Participants | 24 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 20 Participants | 15 Participants | 35 Participants |
| Region of Enrollment United States | 32 participants | 30 participants | 62 participants |
| Sex: Female, Male Female | 19 Participants | 18 Participants | 37 Participants |
| Sex: Female, Male Male | 13 Participants | 12 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 32 | 23 / 30 |
| serious Total, serious adverse events | 3 / 32 | 5 / 30 |
Outcome results
Primary
Change in Mean Methacholine Responsiveness as Assessed by the Provocation Concentration Causing a 20% Fall in Forced Expiratory Volume in One Second (FEV1) (PC20) at Month 3 and 6 Versus Baseline
Our primary outcome was change in airway hyperresponsiveness, as assessed by PC20, from baseline to 3 and/or 6 months of therapy in imatinib treated participants as compared with controls. Change in PC20 was assessed using log2-transformed ratios of PC20 at month 3 and /or month 6 vs PC20 at baseline. Our null hypothesis was that the mean of this ratio will be 0 after log2-transformed. We used a linear mixed-effects model for a repeated-measures analysis to compare the primary outcome between the two groups. PC20 is determined by the provocation concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1).
Time frame: Over 6 months from beginning of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | Change in Mean Methacholine Responsiveness as Assessed by the Provocation Concentration Causing a 20% Fall in Forced Expiratory Volume in One Second (FEV1) (PC20) at Month 3 and 6 Versus Baseline | 1.73 Log2 Ratio | Standard Deviation 0.52 |
| Placebo | Change in Mean Methacholine Responsiveness as Assessed by the Provocation Concentration Causing a 20% Fall in Forced Expiratory Volume in One Second (FEV1) (PC20) at Month 3 and 6 Versus Baseline | 1.07 Log2 Ratio | Standard Deviation 0.6 |
Comparison: Our null hypothesis was that the mean of this ratio will be 0 after log2-transformed.~The target enrollment was 60 assuming 10% drop-out for 54 completions which gave us 80% power to detect a doubling-dose change in PC20.p-value: <0.05Mixed Models Analysis
Secondary
Airway Wall Area
Change in airway wall area as assessed by computerized tomography (CT)
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | Airway Wall Area | 0.0002 % of area | Standard Deviation 0.02 |
| Placebo | Airway Wall Area | 0.0002 % of area | Standard Deviation 0.02 |
p-value: 0.25Regression, Linear
Secondary
Airway Wall Thickness
Change in airway wall thickness as assessed by computerized tomography (CT)
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | Airway Wall Thickness | -0.0040 % of airway | Standard Deviation 0.03 |
| Placebo | Airway Wall Thickness | -0.0027 % of airway | Standard Deviation 0.02 |
p-value: 0.13Regression, Linear
Secondary
Asthma Control Questionnaire (ACQ)
Change in patient-reported ACQ score The six-item Asthma Control Questionnaire (ACQ-6) is a scale from 0 to 6 with a lower value denoting an improvement in asthma control. The minimal important difference is 0.5.
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | Asthma Control Questionnaire (ACQ) | -0.62 units on a scale | Standard Deviation 0.96 |
| Placebo | Asthma Control Questionnaire (ACQ) | -0.49 units on a scale | Standard Deviation 0.89 |
p-value: 0.31Regression, Linear
Secondary
Asthma Quality of Life Questionnaire (AQLQ)
Change in patient-reported Asthma Quality of Life Questionnaire (AQLQ) score The asthma quality of life questionnaire (AQLQ) is a 32-item scale with a range from 1-7 with a higher value denoting improvement. The minimal important difference is 0.5.
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | Asthma Quality of Life Questionnaire (AQLQ) | 0.55 units on a scale | Standard Deviation 1 |
| Placebo | Asthma Quality of Life Questionnaire (AQLQ) | 0.25 units on a scale | Standard Deviation 0.8 |
p-value: 0.11Regression, Linear
Secondary
Asthma Symptom Utility Index (ASUI)
Change in patient reported ASUI score The asthma symptom utility index (ASUI) is a 10-item weighted scale with a range from 0.2 to 1 with a higher value indicating improvement. The minimal important difference is 0.09.
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | Asthma Symptom Utility Index (ASUI) | 0.07 units on a scale | Standard Deviation 0.2 |
| Placebo | Asthma Symptom Utility Index (ASUI) | 0.05 units on a scale | Standard Deviation 0.18 |
p-value: 0.62Regression, Linear
Secondary
BAL Eosinophil %
Change in BAL eosinophil percentage
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | BAL Eosinophil % | 2.55 % eosinophils | Standard Deviation 8.8 |
| Placebo | BAL Eosinophil % | -2.63 % eosinophils | Standard Deviation 10.4 |
p-value: 0.15Regression, Linear
Secondary
BAL Neutrophil %
Change in BAL neutrophil percentage from baseline
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | BAL Neutrophil % | -0.8 % neutrophils | Standard Deviation 5.6 |
| Placebo | BAL Neutrophil % | -0.4 % neutrophils | Standard Deviation 7 |
p-value: 0.57Regression, Linear
Secondary
Blood Eosinophils
Change in blood eosinophil count
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | Blood Eosinophils | -10.2 eosinophils per microliter | Standard Deviation 50.6 |
| Placebo | Blood Eosinophils | -2.6 eosinophils per microliter | Standard Deviation 25.6 |
p-value: 0.94Regression, Linear
Secondary
Bronchoalveolar Lavage (BAL) Fluid Tryptase Level
Change in BAL fluid tryptase levels after 24 weeks of imatinib vs. placebo
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | Bronchoalveolar Lavage (BAL) Fluid Tryptase Level | -0.74 ng/mL | Standard Deviation 2.35 |
| Placebo | Bronchoalveolar Lavage (BAL) Fluid Tryptase Level | 0.43 ng/mL | Standard Deviation 2.19 |
p-value: 0.12Regression, Linear
Secondary
Bronchoalveolar Lavage (BAL) PGD2
Change in bronchoalveolar lavage (BAL) PGD2 levels from baseline at 6 months
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | Bronchoalveolar Lavage (BAL) PGD2 | 12.2 pg/mL | Standard Deviation 57.2 |
| Placebo | Bronchoalveolar Lavage (BAL) PGD2 | -4.2 pg/mL | Standard Deviation 54.4 |
p-value: 0.33Regression, Linear
Secondary
Bronchoalveolar Lavage Cysteinyl Leukotrienes
Change in bronchoalveolar lavage cysteinyl leukotrienes levels from baseline
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | Bronchoalveolar Lavage Cysteinyl Leukotrienes | 3.0 pg/mL | Standard Deviation 37.3 |
| Placebo | Bronchoalveolar Lavage Cysteinyl Leukotrienes | 6.5 pg/mL | Standard Deviation 32.9 |
p-value: 0.56Regression, Linear
Secondary
Bronchoalveolar Lavage Histamine
Change in bronchoalveolar lavage histamine levels from baseline
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | Bronchoalveolar Lavage Histamine | 2.1 nM | Standard Deviation 6.3 |
| Placebo | Bronchoalveolar Lavage Histamine | -1.1 nM | Standard Deviation 13.4 |
p-value: 0.54Regression, Linear
Secondary
Change in Inflammatory Mediators in Exhaled Breath Condensate
Assessment of change in eicosanoids in the exhaled breath condensate
Time frame: baseline to week 24
Population: The exhaled breath condensate was not processed for inflammatory mediators.
Secondary
Change in Maximum Post-Bronchodilator (BD) Forced Expiratory Volume in One Second (FEV1) %
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | Change in Maximum Post-Bronchodilator (BD) Forced Expiratory Volume in One Second (FEV1) % | 0.01 % of predicted | Standard Deviation 0.2 |
| Placebo | Change in Maximum Post-Bronchodilator (BD) Forced Expiratory Volume in One Second (FEV1) % | -0.08 % of predicted | Standard Deviation 0.26 |
p-value: 0.1Regression, Linear
Secondary
Change in Number of Self-Reported Asthma Symptom Free Days
Time frame: baseline to week 24
Population: Self-reported asthma symptom free days were not entered into the study database.
Secondary
Change in Sputum Supernatant Differential, Supernatant Tryptase and IL-13
Change in sputum eosinophil and neutrophil percentage. Change in sputum supernatant tryptase as measured by ELISA. Change in sputum IL-13 level as measured by ELISA.
Time frame: baseline to 24 weeks
Population: Sputum sample slide preparation quality was poor and samples meeting quality control were insufficient for analysis of sputum differential.~Insufficient study funds prevented assessment of sputum tryptase. IL-13 was below the detection limit of assay in sputum supernatant.
Secondary
Endobronchial Biopsy Smooth Muscle Tryptase-positive Mast Cells
Change in the biopsy smooth muscle tryptase-positive mast cells from baseline at 6 months
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | Endobronchial Biopsy Smooth Muscle Tryptase-positive Mast Cells | -102.7 mast cells per mm2 | Standard Deviation 167.9 |
| Placebo | Endobronchial Biopsy Smooth Muscle Tryptase-positive Mast Cells | -79.2 mast cells per mm2 | Standard Deviation 157.3 |
p-value: 0.07Regression, Linear
Secondary
Endobronchial Biopsy Total Tryptase-positive Mast Cells
Change in endobronchial biopsy total tryptase-positive mast cells from baseline at 6 months
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | Endobronchial Biopsy Total Tryptase-positive Mast Cells | -54.2 mast cells per mm2 | Standard Deviation 96.5 |
| Placebo | Endobronchial Biopsy Total Tryptase-positive Mast Cells | -32.3 mast cells per mm2 | Standard Deviation 79.8 |
p-value: 0.11Regression, Linear
Secondary
Evening Peak Flow
Change in patient-reported evening peak flow measurement (L/s)
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | Evening Peak Flow | 8.3 L/second | Standard Deviation 53.6 |
| Placebo | Evening Peak Flow | -8.2 L/second | Standard Deviation 37.2 |
p-value: 0.31Mixed Models Analysis
Secondary
FEV1%
Change in FEV1% of predicted
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | FEV1% | 2.3 % of predicted | Standard Deviation 8.86 |
| Placebo | FEV1% | 0.78 % of predicted | Standard Deviation 13.1 |
Comparison: For FEV1% we used a linear mixed-effects model to assess the between-group difference in the change from baseline over weeks 8-24.p-value: 0.06Mixed Models Analysis
Secondary
FEV1 in Liters
Change in FEV1 in treatment group compared to placebo group
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Imatinib Mesylate | FEV1 in Liters | 0.046 L |
| Placebo | FEV1 in Liters | 0 L |
Comparison: For FEV1 we used a linear mixed-effects model to assess the between-group difference in the change from baseline over weeks 8-24.p-value: <0.05Mixed Models Analysis
Secondary
Fractional Exhaled Nitric Oxide (FeNO)
Change in Fractional Exhaled Nitric Oxide Measurement (ppb)
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | Fractional Exhaled Nitric Oxide (FeNO) | 7.89 parts per billion | Standard Deviation 33 |
| Placebo | Fractional Exhaled Nitric Oxide (FeNO) | -5.92 parts per billion | Standard Deviation 33.2 |
p-value: 0.11Regression, Linear
Secondary
Morning Peak Flow Measurement
Change in patient-reported morning peak flow measurement (L/s)
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | Morning Peak Flow Measurement | 7.3 L/second | Standard Deviation 46.1 |
| Placebo | Morning Peak Flow Measurement | -6.4 L/second | Standard Deviation 39.3 |
p-value: 0.38Mixed Models Analysis
Secondary
Number of Asthma Exacerbations
Number of asthma exacerbations experienced from randomization to study completion.
Time frame: Up to 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Imatinib Mesylate | Number of Asthma Exacerbations | 16 events |
| Placebo | Number of Asthma Exacerbations | 20 events |
p-value: 0.36Poisson regression model
Secondary
Serum Total Tryptase
Change in serum total tryptase after 24 weeks of imatinib vs placebo treatment
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | Serum Total Tryptase | -2.02 ng/ml | Standard Deviation 2.32 |
| Placebo | Serum Total Tryptase | -0.56 ng/ml | Standard Deviation 1.39 |
p-value: <0.05Regression, Linear
Secondary
Urinary Leukotriene E4
Change in urinary leukotriene E4 levels from baseline
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | Urinary Leukotriene E4 | 0.07 ng/mg Creatinine | Standard Deviation 0.65 |
| Placebo | Urinary Leukotriene E4 | 0.01 ng/mg Creatinine | Standard Deviation 0.18 |
p-value: 0.47Regression, Linear
Secondary
Urinary Prostaglandin D2
Change in urinary Prostaglandin D2 levels from baseline
Time frame: 6 months after start of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imatinib Mesylate | Urinary Prostaglandin D2 | -0.30 ng/mg Creatinine | Standard Deviation 1.5 |
| Placebo | Urinary Prostaglandin D2 | 0.39 ng/mg Creatinine | Standard Deviation 1.73 |
p-value: 0.18Regression, Linear