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The study was truncated due to the long period of enrollment and the collection of a sufficient amount of data that allowed the scientific objectives to be met
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To evaluate and compare the expression and change in expression of key severe asthma targets at baseline in mile to moderate asthmatics vs. severe asthmatic subjects.
To evaluate and compare the airway pathology at baseline and changes in airway pathology in relation to asthma severity.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intermittent mild steroid-naïve asthmatic group | Experimental | Asymptomatic subjects receiving only beta-agonist inhaler with predicted FEV1 >=80% and normal peak expiratory flow between attacks will be included. |
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| Mild to moderate persistent asthmatic group | Experimental | Subjects with mild to moderate persistent asthma on low to moderate dose of inhaled corticosteroid (200-500 microgram fluticasone propionate daily or equivalent), an FEV1 >= 80% predicted (post-bronchodilator), and less than 20% variability in peak expiratory flow. |
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| Severe asthma group | Experimental | Subjects with severe persistent asthma. They will be on either: high inhaled corticosteroid (CS >=1000 microgram fluticasone daily or equivalent) or on high dose inhaled CS plus oral CS (no more than 20 milligrams predisolone a day). The subjects should have at least one ( if on oral steroids) or two (if only on inhaled steroids) of the following: 1) FEV1<80% and FEV1/FVC ratio <70% 2) more than 25% variability in peak expiratory flow 3) daily symptoms ± nocturnal symptoms 4) severe exacerbations of >= twice a year in at least one of the last two years. |
|
| Healthy subjects group | Placebo Comparator | Non-asthmatic and non-smokers with FEV1 > 85% predicted, on no regular medication. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Prednisolone | Drug | Subjects will be administered oral prednisolone at a dose of 0.5 mg/kg, up to a maximum of 40 mg per day for 14 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Airway pathology endpoints Target Validation endpoints Biomarker endpoints Clinical endpoints | biomarkers, vital signs, ECG | Through 2 weeks of Prednisolone dosing |
| Measure | Description | Time Frame |
|---|---|---|
| Expression of airway and systemic biomarkers. Relationship between changes in target expression and clinical measures of disease activity. Relationship between steady state plasma exposure of prednisolone and pharmacodynamic biomarkers. | biomarkers | Through 2 weeks of prednisolone dosing. |
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Inclusion criteria:
Exclusion criteria:
In addition, the following additional exclusion criteria must apply to mild to moderate persistent asthmatics on regular inhaled steroids:
In addition, the following additional exclusion criteria must apply to severe persistent asthmatics with clinical controlled asthma symptoms:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Leicester | Leicestershire | LE3 9QP | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29550052 | Derived | Siddiqui S, Shikotra A, Richardson M, Doran E, Choy D, Bell A, Austin CD, Eastham-Anderson J, Hargadon B, Arron JR, Wardlaw A, Brightling CE, Heaney LG, Bradding P. Airway pathological heterogeneity in asthma: Visualization of disease microclusters using topological data analysis. J Allergy Clin Immunol. 2018 Nov;142(5):1457-1468. doi: 10.1016/j.jaci.2017.12.982. Epub 2018 Mar 14. |
| Label | URL |
|---|---|
| Results for study RES100769 can be found on the GSK Clinical Study Register. | View source |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| D011239 | Prednisolone |
| D001999 | Bronchoscopy |
| ID | Term |
|---|---|
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
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| Bronchoscopy | Procedure | All subjects will undergo bronchoscopy assessments which will involve insertion of a standard bronchoscope. |
|
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D000072473 |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D003948 | Diagnostic Techniques, Respiratory System |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D004724 | Endoscopy |
| D003949 | Diagnostic Techniques, Surgical |
| D019060 | Minimally Invasive Surgical Procedures |
| D013514 | Surgical Procedures, Operative |
| D013510 | Pulmonary Surgical Procedures |
| D019616 | Thoracic Surgical Procedures |