REVErsing Airway Remodelling With Tezepelumab

• Status: Not yet recruiting
• Trial end date: 2025-02-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Montpellier

Criteria

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 run-in period

• On CT scan, the average percentage wall area index at the B1 and B8 bronchi (generation 3) 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

• Biological therapy during the past 3 months

• 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