REVErsing Airway Remodelling With Tezepelumab (REVERT)

Inclusion Criteria: 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 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 In stable condition for the 4-week before randomization On CT scan, the average percentage wall area index at the B1 and B8 bronchi (generation 3, 4, 5) is >65% Exclusion Criteria: CT abnormalities evocative of any respiratory condition other than asthma Treatment regimen discordant with best practices Pulmonary disease other than asthma requiring treatment during the previous 12 months A smoking history of >20 pack years Receipt of any marketed or investigational biologic agent§ within 3 months or 5 halflives (whichever is longer) prior to randomization or receipt of any investigational non biologic agent within 30 days or 5 half-lives (whichever is longest) prior to randomization or receipt of live attenuated vaccines 30 days prior to the date of randomization. Participants enrolled in current or previous tezepelumab studies will not be included. Participants on previous biologics treatment are allowed to enter the study provided the appropriate washout period is fulfilled. Absence of signed consent Non-beneficiary of the French social security, single-payer health insurance system Presence of any condition (physical, psychological or other) that might, in the investigator's opinion, hinder study performance The patient is unavailable or unwilling to participate in future visits Potential interference from other studies Protected populations according to the French public health code Male or female patients seeking to conceive a child Women of childbearing potential and fertile men not using birth control method Pregnant, breastfeeding or lactating women History of a clinically significant infection, including upper (URTI) or lower respiratory tract infection (LRTI), requiring treatment with antibiotics or antiviral medications finalised < 2 weeks before randomization. Patients with preexisting serious infections should be treated before initiating therapy with tezepelumab. A helminth parasitic infection diagnosed within 6 months prior to Visit 1 that has not been treated with, or has failed to respond to, standard of care therapy. Patients using vaping products, including electronic cigarettes (because may induce abnormality at CT scan). Bronchial thermoplasty in the last 12 months prior to Visit 1. History of documented immune complex disease (Type III hypersensitivity reactions) following any biologic therapy. History of known immunodeficiency disorder including a positive human immunodeficiency virus test or the participant taking antiretroviral medications as determined by medical history and/or participant's verbal report. Receipt of the T2 cytokine inhibitor Suplatast tosilate within 15 days prior to randomization. Treatment with systemic immunosuppressive/immunomodulating drugs (eg, methotrexate, cyclosporine, etc.), except for OCS used in the treatment of asthma/asthma exacerbations, within the last 12 weeks or 5 half-lives (whichever is longer) prior to randomization. Receipt of immunoglobulin or blood products within 30 days prior to randomization. Receipt of allergen immunotherapy not stable within 30 days prior to randomization or with anticipated change during the treatment period.