CompletedNCT01097694KIAUpdated May 19, 2017Results posted

Effects of cKit Inhibition by Imatinib in Patients With Severe Refractory Asthma (KIA)

A Phase 2 interventional study of Imatinib mesylate and Placebo in Asthma, sponsored by Brigham and Women's Hospital. Completed at 7 sites in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2017-05-19.

Sponsored by Brigham and Women's Hospital · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 176
Allocation: Randomized
Ages: 18 Years to 65 Years
Sex: All

Study 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.

Read the 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.

Conditions studied

Asthma

Browse trials for

Asthma 3,921

Keywords

cKIT inhibition in Asthma
Efficacy of Imatinib in severe resistent asthma.

In context

Asthma

3,921 studies on the registry are indexed under Asthma; 507 are open to participants now.

This study's enrollment of 176 is above the median of 83 across 2,752 interventional studies indexed under Asthma.

Browse Asthma studies →

Lead sponsor

Brigham and Women's Hospital is the lead sponsor of 1,236 studies on the registry; 224 are open to participants now.

Of its 116 completed or terminated interventional studies of FDA-regulated products, 64 (55%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 65 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Patients 18-65 years of age, diagnosed with asthma for at least 1 year;
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

Exclusion Criteria:

Current smoking or smoking history of greater than 10 pack-years
Any other significant respiratory or cardiac disease, or the presence of clinically important comorbidities, including uncontrolled diabetes, uncontrolled coronary artery disease
If subject cannot undergo bronchoscopy procedure due to safety reasons
Previous treatment with Imatinib
A history of acute heart failure or chronic left sided heart failure
Uncontrolled systemic arterial hypertension
History of major bleeding or intracranial hemorrhage
History of immunodeficiency diseases, including HIV
Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
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.
Diagnosis of Hepatitis B or C.
History of alcohol abuse within 6 months of screening.
History of illicit drug abuse within 6 months of screening.
Regular use of anticoagulants (eg: Warfarin Sodium, Coumadin), amiodarone, carbamazepine, Cyclosporine, Rifampicin, or reverse transcriptase inhibitors

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 176 participants (actual)

Study arms

Active comparator
Imatinib mesylate
Group on active imatinib treatment
Drug: Imatinib mesylate
Placebo comparator
Placebo
Group on Placebo treatment
Drug: Placebo

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.
Also known as: Gleevec, Zoleta, Glivec, Ziatir
DrugPlacebo
Placebo

What researchers measure

Primary outcomes

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

Secondary outcomes

Serum Total Tryptase
Change in serum total tryptase after 24 weeks of imatinib vs placebo treatment
Time frame: 6 months after start of treatment
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
Change in Maximum Post-Bronchodilator (BD) Forced Expiratory Volume in One Second (FEV1) %
Time frame: 6 months after start of treatment
Number of Asthma Exacerbations
Number of asthma exacerbations experienced from randomization to study completion.
Time frame: Up to 24 weeks
FEV1 in Liters
Change in FEV1 in treatment group compared to placebo group
Time frame: 6 months after start of treatment
FEV1%
Change in FEV1% of predicted
Time frame: 6 months after start of treatment
Morning Peak Flow Measurement
Change in patient-reported morning peak flow measurement (L/s)
Time frame: 6 months after start of treatment
Evening Peak Flow
Change in patient-reported evening peak flow measurement (L/s)
Time frame: 6 months after start of treatment
Fractional Exhaled Nitric Oxide (FeNO)
Change in Fractional Exhaled Nitric Oxide Measurement (ppb)
Time frame: 6 months after start of treatment
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
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
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
BAL Neutrophil %
Change in BAL neutrophil percentage from baseline
Time frame: 6 months after start of treatment
BAL Eosinophil %
Change in BAL eosinophil percentage
Time frame: 6 months after start of treatment
Bronchoalveolar Lavage (BAL) PGD2
Change in bronchoalveolar lavage (BAL) PGD2 levels from baseline at 6 months
Time frame: 6 months after start of treatment
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
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
Blood Eosinophils
Change in blood eosinophil count
Time frame: 6 months after start of treatment
Airway Wall Thickness
Change in airway wall thickness as assessed by computerized tomography (CT)
Time frame: 6 months after start of treatment
Airway Wall Area
Change in airway wall area as assessed by computerized tomography (CT)
Time frame: 6 months after start of treatment
Bronchoalveolar Lavage Histamine
Change in bronchoalveolar lavage histamine levels from baseline
Time frame: 6 months after start of treatment
Urinary Prostaglandin D2
Change in urinary Prostaglandin D2 levels from baseline
Time frame: 6 months after start of treatment
Bronchoalveolar Lavage Cysteinyl Leukotrienes
Change in bronchoalveolar lavage cysteinyl leukotrienes levels from baseline
Time frame: 6 months after start of treatment
Urinary Leukotriene E4
Change in urinary leukotriene E4 levels from baseline
Time frame: 6 months after start of treatment
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
Change in Inflammatory Mediators in Exhaled Breath Condensate
Assessment of change in eicosanoids in the exhaled breath condensate
Time frame: baseline to week 24
Change in Number of Self-Reported Asthma Symptom Free Days
Time frame: baseline to week 24

Results

Posted May 19, 2017

Participant flow

Subjects were recruited from November 2010 until December 2014 in seven academic medical centers.

Participant flow — Overall Study
Milestone	Imatinib Mesylate	Placebo
Started	32	30
Completed	24	26
Not completed	8	4
Withdrew: Adverse event	5	0
Withdrew: Lost to follow-up	0	3
Withdrew: Withdrawal by subject	3	1

Outcome measures

PrimaryChange 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
Reported as:: Mean · Log2 Ratio

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
Log2 Ratio	Imatinib Mesylate	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	1.73 ± 0.52	1.07 ± 0.60

Statistical analysis

Imatinib Mesylate vs Placebo · Mixed Models Analysis · p = <0.05

SecondarySerum Total Tryptase

Change in serum total tryptase after 24 weeks of imatinib vs placebo treatment

Time frame:: 6 months after start of treatment
Reported as:: Mean · ng/ml

Serum Total Tryptase
ng/ml	Imatinib Mesylate	Placebo
Serum Total Tryptase	-2.02 ± 2.32	-0.56 ± 1.39

Statistical analysis

Imatinib Mesylate vs Placebo · Regression, Linear · p = <0.05Adjusted for baseline.

SecondaryBronchoalveolar 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
Reported as:: Mean · ng/mL

Bronchoalveolar Lavage (BAL) Fluid Tryptase Level
ng/mL	Imatinib Mesylate	Placebo
Bronchoalveolar Lavage (BAL) Fluid Tryptase Level	-0.74 ± 2.35	0.43 ± 2.19

Statistical analysis

Imatinib Mesylate vs Placebo · Regression, Linear · p = 0.12Adjusted for baseline.

SecondaryChange in Maximum Post-Bronchodilator (BD) Forced Expiratory Volume in One Second (FEV1) %

Time frame:: 6 months after start of treatment
Reported as:: Mean · % of predicted

Change in Maximum Post-Bronchodilator (BD) Forced Expiratory Volume in One Second (FEV1) %
% of predicted	Imatinib Mesylate	Placebo
Change in Maximum Post-Bronchodilator (BD) Forced Expiratory Volume in One Second (FEV1) %	0.01 ± 0.2	-0.08 ± 0.26

Statistical analysis

Imatinib Mesylate vs Placebo · Regression, Linear · p = 0.10Adjusted for baseline.

SecondaryNumber of Asthma Exacerbations

Number of asthma exacerbations experienced from randomization to study completion.

Time frame:: Up to 24 weeks
Reported as:: Number · events

Number of Asthma Exacerbations
events	Imatinib Mesylate	Placebo
Number of Asthma Exacerbations	16	20

Statistical analysis

Imatinib Mesylate vs Placebo · Poisson regression model · p = 0.36

SecondaryFEV1 in Liters

Change in FEV1 in treatment group compared to placebo group

Time frame:: 6 months after start of treatment
Reported as:: Mean · L

FEV1 in Liters
L	Imatinib Mesylate	Placebo
FEV1 in Liters	0.046 (0.036 to 0.056)	0 (0 to 0)

Statistical analysis

Imatinib Mesylate vs Placebo · Mixed Models Analysis · p = <0.05adjusted for baseline values

SecondaryFEV1%

Change in FEV1% of predicted

Time frame:: 6 months after start of treatment
Reported as:: Mean · % of predicted

FEV1%
% of predicted	Imatinib Mesylate	Placebo
FEV1%	2.3 ± 8.86	0.78 ± 13.1

Statistical analysis

Imatinib Mesylate vs Placebo · Mixed Models Analysis · p = 0.06Adjusted for baseline.

SecondaryMorning Peak Flow Measurement

Change in patient-reported morning peak flow measurement (L/s)

Time frame:: 6 months after start of treatment
Reported as:: Mean · L/second

Morning Peak Flow Measurement
L/second	Imatinib Mesylate	Placebo
Morning Peak Flow Measurement	7.3 ± 46.1	-6.4 ± 39.3

Statistical analysis

Imatinib Mesylate vs Placebo · Mixed Models Analysis · p = 0.38Adjusted for baseline

SecondaryEvening Peak Flow

Change in patient-reported evening peak flow measurement (L/s)

Time frame:: 6 months after start of treatment
Reported as:: Mean · L/second

Evening Peak Flow
L/second	Imatinib Mesylate	Placebo
Evening Peak Flow	8.3 ± 53.6	-8.2 ± 37.2

Statistical analysis

Imatinib Mesylate vs Placebo · Mixed Models Analysis · p = 0.31Adjusted for baseline.

SecondaryFractional Exhaled Nitric Oxide (FeNO)

Change in Fractional Exhaled Nitric Oxide Measurement (ppb)

Time frame:: 6 months after start of treatment
Reported as:: Mean · parts per billion

Fractional Exhaled Nitric Oxide (FeNO)
parts per billion	Imatinib Mesylate	Placebo
Fractional Exhaled Nitric Oxide (FeNO)	7.89 ± 33.0	-5.92 ± 33.2

Statistical analysis

Imatinib Mesylate vs Placebo · Regression, Linear · p = 0.11Adjusted for baseline

SecondaryAsthma 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
Reported as:: Mean · units on a scale

Asthma Control Questionnaire (ACQ)
units on a scale	Imatinib Mesylate	Placebo
Asthma Control Questionnaire (ACQ)	-0.62 ± 0.96	-0.49 ± 0.89

Statistical analysis

Imatinib Mesylate vs Placebo · Regression, Linear · p = 0.31Adjusted for baseline.

SecondaryAsthma 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
Reported as:: Mean · units on a scale

Asthma Quality of Life Questionnaire (AQLQ)
units on a scale	Imatinib Mesylate	Placebo
Asthma Quality of Life Questionnaire (AQLQ)	0.55 ± 1.0	0.25 ± 0.8

Statistical analysis

Imatinib Mesylate vs Placebo · Regression, Linear · p = 0.11Adjusted for baseline

SecondaryAsthma 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
Reported as:: Mean · units on a scale

Asthma Symptom Utility Index (ASUI)
units on a scale	Imatinib Mesylate	Placebo
Asthma Symptom Utility Index (ASUI)	0.07 ± 0.20	0.05 ± 0.18

Statistical analysis

Imatinib Mesylate vs Placebo · Regression, Linear · p = 0.62Adjusted for baseline.

SecondaryBAL Neutrophil %

Change in BAL neutrophil percentage from baseline

Time frame:: 6 months after start of treatment
Reported as:: Mean · % neutrophils

BAL Neutrophil %
% neutrophils	Imatinib Mesylate	Placebo
BAL Neutrophil %	-0.8 ± 5.6	-0.4 ± 7.0

Statistical analysis

Imatinib Mesylate vs Placebo · Regression, Linear · p = 0.57Adjusted for baseline.

SecondaryBAL Eosinophil %

Change in BAL eosinophil percentage

Time frame:: 6 months after start of treatment
Reported as:: Mean · % eosinophils

BAL Eosinophil %
% eosinophils	Imatinib Mesylate	Placebo
BAL Eosinophil %	2.55 ± 8.8	-2.63 ± 10.4

Statistical analysis

Imatinib Mesylate vs Placebo · Regression, Linear · p = 0.15Adjusted for baseline

SecondaryBronchoalveolar Lavage (BAL) PGD2

Change in bronchoalveolar lavage (BAL) PGD2 levels from baseline at 6 months

Time frame:: 6 months after start of treatment
Reported as:: Mean · pg/mL

Bronchoalveolar Lavage (BAL) PGD2
pg/mL	Imatinib Mesylate	Placebo
Bronchoalveolar Lavage (BAL) PGD2	12.2 ± 57.2	-4.2 ± 54.4

Statistical analysis

Imatinib Mesylate vs Placebo · Regression, Linear · p = 0.33Adjusted for baseline.

SecondaryEndobronchial 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
Reported as:: Mean · mast cells per mm2

Endobronchial Biopsy Total Tryptase-positive Mast Cells
mast cells per mm2	Imatinib Mesylate	Placebo
Endobronchial Biopsy Total Tryptase-positive Mast Cells	-54.2 ± 96.5	-32.3 ± 79.8

Statistical analysis

Imatinib Mesylate vs Placebo · Regression, Linear · p = 0.11Adjusted for baseline.

SecondaryEndobronchial 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
Reported as:: Mean · mast cells per mm2

Endobronchial Biopsy Smooth Muscle Tryptase-positive Mast Cells
mast cells per mm2	Imatinib Mesylate	Placebo
Endobronchial Biopsy Smooth Muscle Tryptase-positive Mast Cells	-102.7 ± 167.9	-79.2 ± 157.3

Statistical analysis

Imatinib Mesylate vs Placebo · Regression, Linear · p = 0.07Adjusted for baseline.

SecondaryBlood Eosinophils

Change in blood eosinophil count

Time frame:: 6 months after start of treatment
Reported as:: Mean · eosinophils per microliter

Blood Eosinophils
eosinophils per microliter	Imatinib Mesylate	Placebo
Blood Eosinophils	-10.2 ± 50.6	-2.6 ± 25.6

Statistical analysis

Imatinib Mesylate vs Placebo · Regression, Linear · p = 0.94Adjusted for baseline.

SecondaryAirway Wall Thickness

Change in airway wall thickness as assessed by computerized tomography (CT)

Time frame:: 6 months after start of treatment
Reported as:: Mean · % of airway

Airway Wall Thickness
% of airway	Imatinib Mesylate	Placebo
Airway Wall Thickness	-0.0040 ± 0.03	-0.0027 ± 0.02

Statistical analysis

Imatinib Mesylate vs Placebo · Regression, Linear · p = 0.13Adjusted for baseline

SecondaryAirway Wall Area

Change in airway wall area as assessed by computerized tomography (CT)

Time frame:: 6 months after start of treatment
Reported as:: Mean · % of area

Airway Wall Area
% of area	Imatinib Mesylate	Placebo
Airway Wall Area	0.0002 ± 0.02	0.0002 ± 0.02

Statistical analysis

Imatinib Mesylate vs Placebo · Regression, Linear · p = 0.25Adjusted for baseline

SecondaryBronchoalveolar Lavage Histamine

Change in bronchoalveolar lavage histamine levels from baseline

Time frame:: 6 months after start of treatment
Reported as:: Mean · nM

Bronchoalveolar Lavage Histamine
nM	Imatinib Mesylate	Placebo
Bronchoalveolar Lavage Histamine	2.1 ± 6.3	-1.1 ± 13.4

Statistical analysis

Imatinib Mesylate vs Placebo · Regression, Linear · p = 0.54Adjusted for baseline.

SecondaryUrinary Prostaglandin D2

Change in urinary Prostaglandin D2 levels from baseline

Time frame:: 6 months after start of treatment
Reported as:: Mean · ng/mg Creatinine

Urinary Prostaglandin D2
ng/mg Creatinine	Imatinib Mesylate	Placebo
Urinary Prostaglandin D2	-0.30 ± 1.5	0.39 ± 1.73

Statistical analysis

Imatinib Mesylate vs Placebo · Regression, Linear · p = 0.18Adjusted for baseline.

SecondaryBronchoalveolar Lavage Cysteinyl Leukotrienes

Change in bronchoalveolar lavage cysteinyl leukotrienes levels from baseline

Time frame:: 6 months after start of treatment
Reported as:: Mean · pg/mL

Bronchoalveolar Lavage Cysteinyl Leukotrienes
pg/mL	Imatinib Mesylate	Placebo
Bronchoalveolar Lavage Cysteinyl Leukotrienes	3.0 ± 37.3	6.5 ± 32.9

Statistical analysis

Imatinib Mesylate vs Placebo · Regression, Linear · p = 0.56Adjusted for baseline.

SecondaryUrinary Leukotriene E4

Change in urinary leukotriene E4 levels from baseline

Time frame:: 6 months after start of treatment
Reported as:: Mean · ng/mg Creatinine

Urinary Leukotriene E4
ng/mg Creatinine	Imatinib Mesylate	Placebo
Urinary Leukotriene E4	0.07 ± 0.65	0.01 ± 0.18

Statistical analysis

Imatinib Mesylate vs Placebo · Regression, Linear · p = 0.47Adjusted for baseline.

SecondaryChange 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

No measurements were reported for this outcome.

SecondaryChange in Inflammatory Mediators in Exhaled Breath Condensate

Assessment of change in eicosanoids in the exhaled breath condensate

Time frame:: baseline to week 24

No measurements were reported for this outcome.

SecondaryChange in Number of Self-Reported Asthma Symptom Free Days

Time frame:: baseline to week 24

No measurements were reported for this outcome.

Adverse events

Collected over Adverse event data were collected from randomization to study drug vs. placebo up to 24 weeks.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Imatinib Mesylate	—	3/32 (9.4%)	29/32 (90.6%)
Placebo	—	5/30 (16.7%)	23/30 (76.7%)

Most frequent serious events

Most frequent serious events
Event	Imatinib Mesylate	Placebo
Asthma ExacerbationRespiratory, thoracic and mediastinal disorders	2/32	3/30
Acute URIInfections and infestations	0/32	1/30
Ankle DislocationMusculoskeletal and connective tissue disorders	0/32	1/30
AngioedemiaImmune system disorders	0/32	1/30
NauseaGastrointestinal disorders	1/32	0/30
LeukocytosisBlood and lymphatic system disorders	1/32	0/30
Leg CrampsMusculoskeletal and connective tissue disorders	1/32	0/30
HypokalemiaMetabolism and nutrition disorders	1/32	0/30

Most frequent other events

Showing 10 of 18

Most frequent other events
Event	Imatinib Mesylate	Placebo
Asthma ExacerbationRespiratory, thoracic and mediastinal disorders	14/32	13/30
Upper Respiratory InfectionRespiratory, thoracic and mediastinal disorders	9/32	12/30
Nausea/VomitingGastrointestinal disorders	6/32	2/30
Muscle CrampsMusculoskeletal and connective tissue disorders	6/32	1/30
DiarrheaGastrointestinal disorders	5/32	2/30
RashSkin and subcutaneous tissue disorders	4/32	3/30
HypophosphatemiaMetabolism and nutrition disorders	4/32	0/30
Back/Shoulder PainMusculoskeletal and connective tissue disorders	0/32	3/30
FatigueGeneral disorders	0/32	2/30
PneumoniaInfections and infestations	0/32	2/30

Baseline characteristics

severe asthmatics ages 18-65

Age, Categorical
Age, Categorical(Participants)	Imatinib Mesylate	Placebo	Total
<=18 years	0	0	0
Between 18 and 65 years	32	30	62
>=65 years	0	0	0

Age, Continuous
Age, Continuous(years)	Imatinib Mesylate	Placebo	Total
Mean	40.2 ± 10.2	37.7 ± 11.8	40.1 ± 11.1

Sex: Female, Male
Sex: Female, Male(Participants)	Imatinib Mesylate	Placebo	Total
Female	19	18	37
Male	13	12	25

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Imatinib Mesylate	Placebo	Total
Hispanic or Latino	5	5	10
Not Hispanic or Latino	27	25	52
Unknown or Not Reported	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Imatinib Mesylate	Placebo	Total
American Indian or Alaska Native	0	0	0
Asian	1	1	2
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	11	13	24
White	20	15	35
More than one race	0	0	0
Unknown or Not Reported	0	1	1

Region of Enrollment
Region of Enrollment(participants)	Imatinib Mesylate	Placebo	Total
United States	32	30	62

Study locations

7 sites

University of Alabama
Birmingham, Alabama 35294, United States
Brigham and Womens Hospital
Boston, Massachusetts 02115, United States
Washington University School of Medicine
Saint Louis, Missouri 63110, United States
Columbia University
New York, New York 10032, United States
Cleveland Clinic
Cleveland, Ohio 44195, United States
Temple University
Philadelphia, Pennsylvania 19140, United States
University of Wisconsin
Madison, Wisconsin 53792, United States

References and documents

Publications

Al-Muhsen SZ, Shablovsky G, Olivenstein R, Mazer B, Hamid Q. The expression of stem cell factor and c-kit receptor in human asthmatic airways. Clin Exp Allergy. 2004 Jun;34(6):911-6. doi: 10.1111/j.1365-2222.2004.01975.x. PubMed 15196279 ↗
Bischoff SC, Dahinden CA. c-kit ligand: a unique potentiator of mediator release by human lung mast cells. J Exp Med. 1992 Jan 1;175(1):237-44. doi: 10.1084/jem.175.1.237. PubMed 1370529 ↗
Brightling CE, Bradding P, Symon FA, Holgate ST, Wardlaw AJ, Pavord ID. Mast-cell infiltration of airway smooth muscle in asthma. N Engl J Med. 2002 May 30;346(22):1699-705. doi: 10.1056/NEJMoa012705. PubMed 12037149 ↗
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Individual participant data

Plan to share: Undecided

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on May 19, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01097694
Lead sponsor: Brigham and Women's Hospital
Collaborators: Baim Institute for Clinical Research, National Heart, Lung, and Blood Institute (NHLBI)
Responsible party: Elliot Israel, MD (Director of the Asthma Research Center, Brigham and Women's Hospital) — Principal investigator
First posted: Apr 2, 2010
Start date: Nov 2010
Primary completion: Aug 2015
Completion: Aug 2016
Results posted: May 19, 2017
Last update: May 19, 2017

Study contacts

Elliot Israel, M.D

principal investigator · Brigham and Womens Hospital

Joshua Boyce, M.D

principal investigator · Brigham and Womens Hospital

Oversight

Data monitoring committee: Yes

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Effects of cKit Inhibition by Imatinib in Patients With Severe Refractory Asthma (KIA)

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