Ignite Creation Date:
2025-12-25 @ 2:00 AM
Ignite Modification Date:
2025-12-26 @ 2:01 AM
Study NCT ID:
NCT01097694
Status:
COMPLETED
Last Update Posted:
2017-05-19
First Post:
2010-03-23
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Effects of cKit Inhibition by Imatinib in Patients With Severe Refractory Asthma (KIA)
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001249', 'term': 'Asthma'}], 'ancestors': [{'id': 'D001982', 'term': 'Bronchial Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D008173', 'term': 'Lung Diseases, Obstructive'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012130', 'term': 'Respiratory Hypersensitivity'}, {'id': 'D006969', 'term': 'Hypersensitivity, Immediate'}, {'id': 'D006967', 'term': 'Hypersensitivity'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000068877', 'term': 'Imatinib Mesylate'}], 'ancestors': [{'id': 'D001549', 'term': 'Benzamides'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D001565', 'term': 'Benzoates'}, {'id': 'D000146', 'term': 'Acids, Carbocyclic'}, {'id': 'D002264', 'term': 'Carboxylic Acids'}, {'id': 'D001555', 'term': 'Benzene Derivatives'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D010879', 'term': 'Piperazines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D011743', 'term': 'Pyrimidines'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'eisrael@partners.org', 'phone': '617-732-8110', 'title': 'Elliot Israel, MD', 'organization': "Brigham and Women's Hopsital"}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': 'Adverse event data were collected from randomization to study drug vs. placebo up to 24 weeks.', 'eventGroups': [{'id': 'EG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.', 'otherNumAtRisk': 32, 'otherNumAffected': 29, 'seriousNumAtRisk': 32, 'seriousNumAffected': 3}, {'id': 'EG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo', 'otherNumAtRisk': 30, 'otherNumAffected': 23, 'seriousNumAtRisk': 30, 'seriousNumAffected': 5}], 'otherEvents': [{'term': 'Leukopenia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Rash', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 4, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 4, 'numAffected': 3}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Pruritis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 6, 'numAffected': 5}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Nausea/Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 7, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Upper Respiratory Infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 11, 'numAffected': 9}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 18, 'numAffected': 12}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Pneumonia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Urinary Tract Infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Gastroenteritis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Hypophosphatemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 6, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Hypokalemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Abnormal LFTs', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Muscle Cramps', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 10, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Lightheadedness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Back/Shoulder Pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Asthma Exacerbation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 16, 'numAffected': 14}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 20, 'numAffected': 13}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'seriousEvents': [{'term': 'Asthma Exacerbation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 6, 'numAffected': 3}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Leukocytosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Leg Cramps', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Hypokalemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Acute URI', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Ankle Dislocation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Angioedemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 32, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 30, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Immune system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': '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', 'denoms': [{'units': 'Participants', 'counts': [{'value': '24', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '1.73', 'spread': '0.52', 'groupId': 'OG000'}, {'value': '1.07', 'spread': '0.60', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.05', 'groupIds': ['OG000', 'OG001'], 'groupDescription': 'Our null hypothesis was that the mean of this ratio will be 0 after log2-transformed.\n\nThe target enrollment was 60 assuming 10% drop-out for 54 completions which gave us 80% power to detect a doubling-dose change in PC20.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'Over 6 months from beginning of treatment', 'description': '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.\n\nPC20 is determined by the provocation concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1).', 'unitOfMeasure': 'Log2 Ratio', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Serum Total Tryptase', 'denoms': [{'units': 'Participants', 'counts': [{'value': '19', 'groupId': 'OG000'}, {'value': '23', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '-2.02', 'spread': '2.32', 'groupId': 'OG000'}, {'value': '-0.56', 'spread': '1.39', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.05', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline.'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': 'Change in serum total tryptase after 24 weeks of imatinib vs placebo treatment', 'unitOfMeasure': 'ng/ml', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Bronchoalveolar Lavage (BAL) Fluid Tryptase Level', 'denoms': [{'units': 'Participants', 'counts': [{'value': '21', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.74', 'spread': '2.35', 'groupId': 'OG000'}, {'value': '0.43', 'spread': '2.19', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.12', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline.'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': 'Change in BAL fluid tryptase levels after 24 weeks of imatinib vs. placebo', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Maximum Post-Bronchodilator (BD) Forced Expiratory Volume in One Second (FEV1) %', 'denoms': [{'units': 'Participants', 'counts': [{'value': '24', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '0.01', 'spread': '0.2', 'groupId': 'OG000'}, {'value': '-0.08', 'spread': '0.26', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.10', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline.'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'unitOfMeasure': '% of predicted', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Asthma Exacerbations', 'denoms': [{'units': 'Participants', 'counts': [{'value': '32', 'groupId': 'OG000'}, {'value': '30', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '16', 'groupId': 'OG000'}, {'value': '20', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.36', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Poisson regression model', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'NUMBER', 'timeFrame': 'Up to 24 weeks', 'description': 'Number of asthma exacerbations experienced from randomization to study completion.', 'unitOfMeasure': 'events', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'FEV1 in Liters', 'denoms': [{'units': 'Participants', 'counts': [{'value': '32', 'groupId': 'OG000'}, {'value': '30', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '0.046', 'groupId': 'OG000', 'lowerLimit': '0.036', 'upperLimit': '0.056'}, {'value': '0', 'groupId': 'OG001', 'lowerLimit': '0', 'upperLimit': '0'}]}]}], 'analyses': [{'pValue': '<0.05', 'groupIds': ['OG000', 'OG001'], 'groupDescription': 'For FEV1 we used a linear mixed-effects model to assess the between-group difference in the change from baseline over weeks 8-24.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'adjusted for baseline values'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': 'Change in FEV1 in treatment group compared to placebo group', 'unitOfMeasure': 'L', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'FEV1%', 'denoms': [{'units': 'Participants', 'counts': [{'value': '24', 'groupId': 'OG000'}, {'value': '27', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '2.3', 'spread': '8.86', 'groupId': 'OG000'}, {'value': '0.78', 'spread': '13.1', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.06', 'groupIds': ['OG000', 'OG001'], 'groupDescription': 'For FEV1% we used a linear mixed-effects model to assess the between-group difference in the change from baseline over weeks 8-24.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline.'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': 'Change in FEV1% of predicted', 'unitOfMeasure': '% of predicted', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Morning Peak Flow Measurement', 'denoms': [{'units': 'Participants', 'counts': [{'value': '19', 'groupId': 'OG000'}, {'value': '20', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '7.3', 'spread': '46.1', 'groupId': 'OG000'}, {'value': '-6.4', 'spread': '39.3', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.38', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': 'Change in patient-reported morning peak flow measurement (L/s)', 'unitOfMeasure': 'L/second', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Evening Peak Flow', 'denoms': [{'units': 'Participants', 'counts': [{'value': '19', 'groupId': 'OG000'}, {'value': '20', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '8.3', 'spread': '53.6', 'groupId': 'OG000'}, {'value': '-8.2', 'spread': '37.2', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.31', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline.'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': 'Change in patient-reported evening peak flow measurement (L/s)', 'unitOfMeasure': 'L/second', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Fractional Exhaled Nitric Oxide (FeNO)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}, {'value': '24', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '7.89', 'spread': '33.0', 'groupId': 'OG000'}, {'value': '-5.92', 'spread': '33.2', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.11', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': 'Change in Fractional Exhaled Nitric Oxide Measurement (ppb)', 'unitOfMeasure': 'parts per billion', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Asthma Control Questionnaire (ACQ)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '24', 'groupId': 'OG000'}, {'value': '27', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.62', 'spread': '0.96', 'groupId': 'OG000'}, {'value': '-0.49', 'spread': '0.89', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.31', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline.'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': '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.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Asthma Quality of Life Questionnaire (AQLQ)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '24', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '0.55', 'spread': '1.0', 'groupId': 'OG000'}, {'value': '0.25', 'spread': '0.8', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.11', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': '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.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Asthma Symptom Utility Index (ASUI)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '24', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '0.07', 'spread': '0.20', 'groupId': 'OG000'}, {'value': '0.05', 'spread': '0.18', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.62', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline.'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': '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.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'BAL Neutrophil %', 'denoms': [{'units': 'Participants', 'counts': [{'value': '17', 'groupId': 'OG000'}, {'value': '20', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.8', 'spread': '5.6', 'groupId': 'OG000'}, {'value': '-0.4', 'spread': '7.0', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.57', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline.'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': 'Change in BAL neutrophil percentage from baseline', 'unitOfMeasure': '% neutrophils', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'BAL Eosinophil %', 'denoms': [{'units': 'Participants', 'counts': [{'value': '17', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '2.55', 'spread': '8.8', 'groupId': 'OG000'}, {'value': '-2.63', 'spread': '10.4', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.15', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': 'Change in BAL eosinophil percentage', 'unitOfMeasure': '% eosinophils', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Bronchoalveolar Lavage (BAL) PGD2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '21', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '12.2', 'spread': '57.2', 'groupId': 'OG000'}, {'value': '-4.2', 'spread': '54.4', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.33', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline.'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': 'Change in bronchoalveolar lavage (BAL) PGD2 levels from baseline at 6 months', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Endobronchial Biopsy Total Tryptase-positive Mast Cells', 'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '-54.2', 'spread': '96.5', 'groupId': 'OG000'}, {'value': '-32.3', 'spread': '79.8', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.11', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline.'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': 'Change in endobronchial biopsy total tryptase-positive mast cells from baseline at 6 months', 'unitOfMeasure': 'mast cells per mm2', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Endobronchial Biopsy Smooth Muscle Tryptase-positive Mast Cells', 'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '-102.7', 'spread': '167.9', 'groupId': 'OG000'}, {'value': '-79.2', 'spread': '157.3', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.07', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline.'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': 'Change in the biopsy smooth muscle tryptase-positive mast cells from baseline at 6 months', 'unitOfMeasure': 'mast cells per mm2', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Blood Eosinophils', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '20', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '-10.2', 'spread': '50.6', 'groupId': 'OG000'}, {'value': '-2.6', 'spread': '25.6', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.94', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline.'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': 'Change in blood eosinophil count', 'unitOfMeasure': 'eosinophils per microliter', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Airway Wall Thickness', 'denoms': [{'units': 'Participants', 'counts': [{'value': '21', 'groupId': 'OG000'}, {'value': '27', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.0040', 'spread': '0.03', 'groupId': 'OG000'}, {'value': '-0.0027', 'spread': '0.02', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.13', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': 'Change in airway wall thickness as assessed by computerized tomography (CT)', 'unitOfMeasure': '% of airway', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Airway Wall Area', 'denoms': [{'units': 'Participants', 'counts': [{'value': '21', 'groupId': 'OG000'}, {'value': '27', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '0.0002', 'spread': '0.02', 'groupId': 'OG000'}, {'value': '0.0002', 'spread': '0.02', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.25', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': 'Change in airway wall area as assessed by computerized tomography (CT)', 'unitOfMeasure': '% of area', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Bronchoalveolar Lavage Histamine', 'denoms': [{'units': 'Participants', 'counts': [{'value': '21', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '2.1', 'spread': '6.3', 'groupId': 'OG000'}, {'value': '-1.1', 'spread': '13.4', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.54', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline.'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': 'Change in bronchoalveolar lavage histamine levels from baseline', 'unitOfMeasure': 'nM', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Urinary Prostaglandin D2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '20', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.30', 'spread': '1.5', 'groupId': 'OG000'}, {'value': '0.39', 'spread': '1.73', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.18', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline.'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': 'Change in urinary Prostaglandin D2 levels from baseline', 'unitOfMeasure': 'ng/mg Creatinine', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Bronchoalveolar Lavage Cysteinyl Leukotrienes', 'denoms': [{'units': 'Participants', 'counts': [{'value': '21', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '3.0', 'spread': '37.3', 'groupId': 'OG000'}, {'value': '6.5', 'spread': '32.9', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.56', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline.'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': 'Change in bronchoalveolar lavage cysteinyl leukotrienes levels from baseline', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Urinary Leukotriene E4', 'denoms': [{'units': 'Participants', 'counts': [{'value': '17', 'groupId': 'OG000'}, {'value': '13', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'classes': [{'categories': [{'measurements': [{'value': '0.07', 'spread': '0.65', 'groupId': 'OG000'}, {'value': '0.01', 'spread': '0.18', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.47', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Adjusted for baseline.'}], 'paramType': 'MEAN', 'timeFrame': '6 months after start of treatment', 'description': 'Change in urinary leukotriene E4 levels from baseline', 'unitOfMeasure': 'ng/mg Creatinine', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Sputum Supernatant Differential, Supernatant Tryptase and IL-13', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'timeFrame': 'baseline to 24 weeks', 'description': '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.', 'reportingStatus': 'POSTED', 'populationDescription': 'Sputum sample slide preparation quality was poor and samples meeting quality control were insufficient for analysis of sputum differential.\n\nInsufficient study funds prevented assessment of sputum tryptase. IL-13 was below the detection limit of assay in sputum supernatant.'}, {'type': 'SECONDARY', 'title': 'Change in Inflammatory Mediators in Exhaled Breath Condensate', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'timeFrame': 'baseline to week 24', 'description': 'Assessment of change in eicosanoids in the exhaled breath condensate', 'reportingStatus': 'POSTED', 'populationDescription': 'The exhaled breath condensate was not processed for inflammatory mediators.'}, {'type': 'SECONDARY', 'title': 'Change in Number of Self-Reported Asthma Symptom Free Days', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'timeFrame': 'baseline to week 24', 'reportingStatus': 'POSTED', 'populationDescription': 'Self-reported asthma symptom free days were not entered into the study database.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'FG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '32'}, {'groupId': 'FG001', 'numSubjects': '30'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '24'}, {'groupId': 'FG001', 'numSubjects': '26'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '8'}, {'groupId': 'FG001', 'numSubjects': '4'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '5'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '3'}]}, {'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}], 'recruitmentDetails': 'Subjects were recruited from November 2010 until December 2014 in seven academic medical centers.', 'preAssignmentDetails': '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.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '32', 'groupId': 'BG000'}, {'value': '30', 'groupId': 'BG001'}, {'value': '62', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Imatinib Mesylate', 'description': 'Group on active imatinib treatment\n\nImatinib 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.'}, {'id': 'BG001', 'title': 'Placebo', 'description': 'Group on Placebo treatment\n\nPlacebo: Placebo'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '32', 'groupId': 'BG000'}, {'value': '30', 'groupId': 'BG001'}, {'value': '62', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '40.2', 'spread': '10.2', 'groupId': 'BG000'}, {'value': '37.7', 'spread': '11.8', 'groupId': 'BG001'}, {'value': '40.1', 'spread': '11.1', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '19', 'groupId': 'BG000'}, {'value': '18', 'groupId': 'BG001'}, {'value': '37', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '13', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '25', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '5', 'groupId': 'BG001'}, {'value': '10', 'groupId': 'BG002'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '27', 'groupId': 'BG000'}, {'value': '25', 'groupId': 'BG001'}, {'value': '52', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Asian', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Black or African American', 'measurements': [{'value': '11', 'groupId': 'BG000'}, {'value': '13', 'groupId': 'BG001'}, {'value': '24', 'groupId': 'BG002'}]}, {'title': 'White', 'measurements': [{'value': '20', 'groupId': 'BG000'}, {'value': '15', 'groupId': 'BG001'}, {'value': '35', 'groupId': 'BG002'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '32', 'groupId': 'BG000'}, {'value': '30', 'groupId': 'BG001'}, {'value': '62', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}], 'populationDescription': 'severe asthmatics ages 18-65'}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 176}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2010-11'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-05', 'completionDateStruct': {'date': '2016-08', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2017-05-15', 'studyFirstSubmitDate': '2010-03-23', 'resultsFirstSubmitDate': '2017-04-04', 'studyFirstSubmitQcDate': '2010-03-31', 'lastUpdatePostDateStruct': {'date': '2017-05-19', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2017-05-15', 'studyFirstPostDateStruct': {'date': '2010-04-02', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2017-05-19', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2015-08', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': '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', 'timeFrame': 'Over 6 months from beginning of treatment', 'description': '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.\n\nPC20 is determined by the provocation concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1).'}], 'secondaryOutcomes': [{'measure': 'Serum Total Tryptase', 'timeFrame': '6 months after start of treatment', 'description': 'Change in serum total tryptase after 24 weeks of imatinib vs placebo treatment'}, {'measure': 'Bronchoalveolar Lavage (BAL) Fluid Tryptase Level', 'timeFrame': '6 months after start of treatment', 'description': 'Change in BAL fluid tryptase levels after 24 weeks of imatinib vs. placebo'}, {'measure': 'Change in Maximum Post-Bronchodilator (BD) Forced Expiratory Volume in One Second (FEV1) %', 'timeFrame': '6 months after start of treatment'}, {'measure': 'Number of Asthma Exacerbations', 'timeFrame': 'Up to 24 weeks', 'description': 'Number of asthma exacerbations experienced from randomization to study completion.'}, {'measure': 'FEV1 in Liters', 'timeFrame': '6 months after start of treatment', 'description': 'Change in FEV1 in treatment group compared to placebo group'}, {'measure': 'FEV1%', 'timeFrame': '6 months after start of treatment', 'description': 'Change in FEV1% of predicted'}, {'measure': 'Morning Peak Flow Measurement', 'timeFrame': '6 months after start of treatment', 'description': 'Change in patient-reported morning peak flow measurement (L/s)'}, {'measure': 'Evening Peak Flow', 'timeFrame': '6 months after start of treatment', 'description': 'Change in patient-reported evening peak flow measurement (L/s)'}, {'measure': 'Fractional Exhaled Nitric Oxide (FeNO)', 'timeFrame': '6 months after start of treatment', 'description': 'Change in Fractional Exhaled Nitric Oxide Measurement (ppb)'}, {'measure': 'Asthma Control Questionnaire (ACQ)', 'timeFrame': '6 months after start of treatment', 'description': '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.'}, {'measure': 'Asthma Quality of Life Questionnaire (AQLQ)', 'timeFrame': '6 months after start of treatment', 'description': '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.'}, {'measure': 'Asthma Symptom Utility Index (ASUI)', 'timeFrame': '6 months after start of treatment', 'description': '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.'}, {'measure': 'BAL Neutrophil %', 'timeFrame': '6 months after start of treatment', 'description': 'Change in BAL neutrophil percentage from baseline'}, {'measure': 'BAL Eosinophil %', 'timeFrame': '6 months after start of treatment', 'description': 'Change in BAL eosinophil percentage'}, {'measure': 'Bronchoalveolar Lavage (BAL) PGD2', 'timeFrame': '6 months after start of treatment', 'description': 'Change in bronchoalveolar lavage (BAL) PGD2 levels from baseline at 6 months'}, {'measure': 'Endobronchial Biopsy Total Tryptase-positive Mast Cells', 'timeFrame': '6 months after start of treatment', 'description': 'Change in endobronchial biopsy total tryptase-positive mast cells from baseline at 6 months'}, {'measure': 'Endobronchial Biopsy Smooth Muscle Tryptase-positive Mast Cells', 'timeFrame': '6 months after start of treatment', 'description': 'Change in the biopsy smooth muscle tryptase-positive mast cells from baseline at 6 months'}, {'measure': 'Blood Eosinophils', 'timeFrame': '6 months after start of treatment', 'description': 'Change in blood eosinophil count'}, {'measure': 'Airway Wall Thickness', 'timeFrame': '6 months after start of treatment', 'description': 'Change in airway wall thickness as assessed by computerized tomography (CT)'}, {'measure': 'Airway Wall Area', 'timeFrame': '6 months after start of treatment', 'description': 'Change in airway wall area as assessed by computerized tomography (CT)'}, {'measure': 'Bronchoalveolar Lavage Histamine', 'timeFrame': '6 months after start of treatment', 'description': 'Change in bronchoalveolar lavage histamine levels from baseline'}, {'measure': 'Urinary Prostaglandin D2', 'timeFrame': '6 months after start of treatment', 'description': 'Change in urinary Prostaglandin D2 levels from baseline'}, {'measure': 'Bronchoalveolar Lavage Cysteinyl Leukotrienes', 'timeFrame': '6 months after start of treatment', 'description': 'Change in bronchoalveolar lavage cysteinyl leukotrienes levels from baseline'}, {'measure': 'Urinary Leukotriene E4', 'timeFrame': '6 months after start of treatment', 'description': 'Change in urinary leukotriene E4 levels from baseline'}, {'measure': 'Change in Sputum Supernatant Differential, Supernatant Tryptase and IL-13', 'timeFrame': 'baseline to 24 weeks', 'description': '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.'}, {'measure': 'Change in Inflammatory Mediators in Exhaled Breath Condensate', 'timeFrame': 'baseline to week 24', 'description': 'Assessment of change in eicosanoids in the exhaled breath condensate'}, {'measure': 'Change in Number of Self-Reported Asthma Symptom Free Days', 'timeFrame': 'baseline to week 24'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['cKIT inhibition in Asthma', 'Efficacy of Imatinib in severe resistent asthma.'], 'conditions': ['Asthma']}, 'referencesModule': {'references': [{'pmid': '15196279', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '1370529', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '12037149', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '10233863', 'type': 'BACKGROUND', 'citation': 'Campbell E, Hogaboam C, Lincoln P, Lukacs NW. Stem cell factor-induced airway hyperreactivity in allergic and normal mice. Am J Pathol. 1999 Apr;154(4):1259-65. doi: 10.1016/S0002-9440(10)65377-1.'}, {'pmid': '12149526', 'type': 'BACKGROUND', 'citation': 'Carroll NG, Mutavdzic S, James AL. Increased mast cells and neutrophils in submucosal mucous glands and mucus plugging in patients with asthma. Thorax. 2002 Aug;57(8):677-82. doi: 10.1136/thorax.57.8.677.'}, {'pmid': '17872493', 'type': 'BACKGROUND', 'citation': 'Flood-Page P, Swenson C, Faiferman I, Matthews J, Williams M, Brannick L, Robinson D, Wenzel S, Busse W, Hansel TT, Barnes NC; International Mepolizumab Study Group. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med. 2007 Dec 1;176(11):1062-71. doi: 10.1164/rccm.200701-085OC. Epub 2007 Sep 13.'}, {'pmid': '11112161', 'type': 'BACKGROUND', 'citation': 'Proceedings of the ATS workshop on refractory asthma: current understanding, recommendations, and unanswered questions. American Thoracic Society. Am J Respir Crit Care Med. 2000 Dec;162(6):2341-51. doi: 10.1164/ajrccm.162.6.ats9-00. No abstract available.'}, {'pmid': '8630386', 'type': 'BACKGROUND', 'citation': 'Lukacs NW, Kunkel SL, Strieter RM, Evanoff HL, Kunkel RG, Key ML, Taub DD. The role of stem cell factor (c-kit ligand) and inflammatory cytokines in pulmonary mast cell activation. Blood. 1996 Mar 15;87(6):2262-8.'}, {'pmid': '19264687', 'type': 'BACKGROUND', 'citation': "Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, Hargreave FE, O'Byrne PM. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med. 2009 Mar 5;360(10):985-93. doi: 10.1056/NEJMoa0805435."}, {'pmid': '16483568', 'type': 'BACKGROUND', 'citation': 'Reber L, Da Silva CA, Frossard N. Stem cell factor and its receptor c-Kit as targets for inflammatory diseases. Eur J Pharmacol. 2006 Mar 8;533(1-3):327-40. doi: 10.1016/j.ejphar.2005.12.067. Epub 2006 Feb 17.'}, {'pmid': '9221761', 'type': 'BACKGROUND', 'citation': 'Yuan Q, Austen KF, Friend DS, Heidtman M, Boyce JA. Human peripheral blood eosinophils express a functional c-kit receptor for stem cell factor that stimulates very late antigen 4 (VLA-4)-mediated cell adhesion to fibronectin and vascular cell adhesion molecule 1 (VCAM-1). J Exp Med. 1997 Jul 21;186(2):313-23. doi: 10.1084/jem.186.2.313.'}, {'pmid': '28514613', 'type': 'DERIVED', 'citation': 'Cahill KN, Katz HR, Cui J, Lai J, Kazani S, Crosby-Thompson A, Garofalo D, Castro M, Jarjour N, DiMango E, Erzurum S, Trevor JL, Shenoy K, Chinchilli VM, Wechsler ME, Laidlaw TM, Boyce JA, Israel E. KIT Inhibition by Imatinib in Patients with Severe Refractory Asthma. N Engl J Med. 2017 May 18;376(20):1911-1920. doi: 10.1056/NEJMoa1613125.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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?\n\nSpecific Aims of the study are:\n\nSpecific 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.\n\nPatients 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.\n\nSpecific 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Patients 18-65 years of age, diagnosed with asthma for at least 1 year;\n2. 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)\n\nExclusion Criteria:\n\n1. Current smoking or smoking history of greater than 10 pack-years\n2. Any other significant respiratory or cardiac disease, or the presence of clinically important comorbidities, including uncontrolled diabetes, uncontrolled coronary artery disease\n3. If subject cannot undergo bronchoscopy procedure due to safety reasons\n4. Previous treatment with Imatinib\n5. A history of acute heart failure or chronic left sided heart failure\n6. Uncontrolled systemic arterial hypertension\n7. History of major bleeding or intracranial hemorrhage\n8. History of immunodeficiency diseases, including HIV\n9. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer\n10. 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.\n11. Diagnosis of Hepatitis B or C.\n12. History of alcohol abuse within 6 months of screening.\n13. History of illicit drug abuse within 6 months of screening.\n14. Regular use of anticoagulants (eg: Warfarin Sodium, Coumadin), amiodarone, carbamazepine, Cyclosporine, Rifampicin, or reverse transcriptase inhibitors'}, 'identificationModule': {'nctId': 'NCT01097694', 'acronym': 'KIA', 'briefTitle': 'Effects of cKit Inhibition by Imatinib in Patients With Severe Refractory Asthma (KIA)', 'organization': {'class': 'OTHER', 'fullName': "Brigham and Women's Hospital"}, 'officialTitle': 'A 28 Week, Treatment Randomized, Double -Blind, Placebo-controlled Study of the Effects of cKit Inhibition by Imatinib in Patients With Severe Refractory Asthma (KIA)', 'orgStudyIdInfo': {'id': '2010P000170'}, 'secondaryIdInfos': [{'id': 'U01HL102225', 'link': 'https://reporter.nih.gov/quickSearch/U01HL102225', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Imatinib mesylate', 'description': 'Group on active imatinib treatment', 'interventionNames': ['Drug: Imatinib mesylate']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Group on Placebo treatment', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Imatinib mesylate', 'type': 'DRUG', 'otherNames': ['Gleevec, Zoleta, Glivec, Ziatir'], 'description': '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.', 'armGroupLabels': ['Imatinib mesylate']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'Placebo', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '35294', 'city': 'Birmingham', 'state': 'Alabama', 'country': 'United States', 'facility': 'University of Alabama', 'geoPoint': {'lat': 33.52066, 'lon': -86.80249}}, {'zip': '02115', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': 'Brigham and Womens Hospital', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '63110', 'city': 'St Louis', 'state': 'Missouri', 'country': 'United States', 'facility': 'Washington University School of Medicine', 'geoPoint': {'lat': 38.62727, 'lon': -90.19789}}, {'zip': '10032', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Columbia University', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '44195', 'city': 'Cleveland', 'state': 'Ohio', 'country': 'United States', 'facility': 'Cleveland Clinic', 'geoPoint': {'lat': 41.4995, 'lon': -81.69541}}, {'zip': '19140', 'city': 'Philadelphia', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'Temple University', 'geoPoint': {'lat': 39.95238, 'lon': -75.16362}}, {'zip': '53792', 'city': 'Madison', 'state': 'Wisconsin', 'country': 'United States', 'facility': 'University of Wisconsin', 'geoPoint': {'lat': 43.07305, 'lon': -89.40123}}], 'overallOfficials': [{'name': 'Elliot Israel, M.D', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Brigham and Womens Hospital'}, {'name': 'Joshua Boyce, M.D', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Brigham and Womens Hospital'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': "Brigham and Women's Hospital", 'class': 'OTHER'}, 'collaborators': [{'name': 'Baim Institute for Clinical Research', 'class': 'OTHER'}, {'name': 'National Heart, Lung, and Blood Institute (NHLBI)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Director of the Asthma Research Center', 'investigatorFullName': 'Elliot Israel, MD', 'investigatorAffiliation': "Brigham and Women's Hospital"}}}}