REVErsing Airway Remodelling With Tezepelumab : a Protocol for a Double-blind Randomized Controlled Trial for Patients With Asthma
The aim of this protocol is to perform a first randomized controlled trial evaluating how Tezepelumab affects the bronchial morphology (and computed tomographic variables in general) of asthmatic patients. In parallel, the investigators also hope to reproduce clinical benefits and perform a transcriptomic study that will juxtapose changes in genetic expression with changes in bronchial morphology and inflammatory signatures. The general hypothesis is that tezepelumab treatment is capable of at least partially reversing bronchial remodelling as detected on computed-tomographic (CT) scans. The investigators also expect such reversal to occur within a unique physiological repair environment that will be reflected by transcriptomic profiles
⁃ Admitted to screening visit:
• Minimum age: 18
• Maximum age: 85
• Able to perform an inspiratory and expiratory thoracic computed tomography (CT) scan, plus a nasal CT
• In stable condition for CT scan
• Physician-diagnosed asthma according to GINA criteria
• Disease with clinical impact: at least 1 severe or 2 moderate exacerbations in the previous 12 months despite treatment according to the best standards of care
• Maximal inhaled therapy comprising high dose ICS and at least a second controller according to GINA
⁃ Based on results of screening visit and run-in:
• Post-bronchodilator forced expiratory volume in 1 second (FEV1) predicted values must be at 25-90%
• Asthma Control Questionnaire 6 (ACQ6) \> 1.5
• Oral corticosteroid maintenance therapy (if used) ≤7.5 mg/day
• On CT scan, the average percentage wall area index at the B1 and B8 bronchi (generation 3, 4, 5) is \>65%