A Two-arm, Placebo-controlled, Randomized Clinical Trial to Evaluate the Effect of Tezepelumab on Airway Structure and Function in Patients With Uncontrolled Moderate-to-severe Asthma
In adult patients with uncontrolled moderate-to-severe asthma, blocking TSLP with tezepelumab will improve ventilation heterogeneity (evaluated by hyperpolarized 129Xe MRI), and this will be associated with reduced airway inflammation (evaluated by sputum composition), luminal narrowing and plugging (evaluated by CT).
• General
‣ Able and willing to provide written informed consent.
⁃ Able and willing to comply with the study protocol.
⁃ Males and females ≥ 18 years of age.
• Asthma-related
‣ Asthma diagnosed by a respiratory physician ≥12 months prior to study enrolment based on the Global Initiative for Asthma (GINA) 2021 guidelines.
⁃ ACQ ≥1.5 at screening.
⁃ Methacholine PC20 ≤ 4 mg/mL OR ≥15% decrease in FEV1 during saline inhalation for sputum induction OR ≥15% improvement in FEV1 after bronchodilator during the screening period.
⁃ Criteria met for moderate or severe asthma defined by GINA 2021 guidelines, i.e. treatment with low, medium or high dose ICS (\<250 mcg, 251 - 500 mcg, \>500 mcg of fluticasone equivalent/day respectively) plus another controller. Patients on prednisone would not be excluded, as long as they meet the rest of the inclusion criteria.
⁃ FeNO \>25 ppb OR ≥3% sputum eosinophils (preferred) OR blood eos ≥300/µL during the screening period.
⁃ History of ≥1 exacerbation in the previous year.