Tezepelumab and Methacholine Airway Hyperresponsiveness in Participants With Mild Allergic Asthma

The proposed study will address whether tezepelumab has the unique ability to improve AHR in participants with mild allergic asthma. This is a phase 2 multi-centre randomized double-blind placebo-controlled parallel-group study to examine the effects of 24 weeks tezepelumab 210 mg sc q4wks on methacholine airway hyperresponsiveness in participants with mild allergic asthma, stratified for sex and sensitivity to seasonal allergens. There are 9 study visits over a period of 27 weeks (Figure 1). Study procedures performed at Weeks -1, 8, 16 and 24 will be divided across 2 visits at least 48 hours apart for measurement of AHR to methacholine first, and mannitol at least 48 hours later. The screening period at Week -1 will determine eligibility. At Week -1, eligible allergic mild asthmatic participants will be randomized 1:1 to placebo or tezepelumab 210 mg subcutaneous administered monthly for a total of 24 weeks. AHR will be measured by methacholine and mannitol challenges at baseline (Week -1) performed at least 48 hours apart. Changes in AHR response will be measured by repeat methacholine and mannitol challenges at Weeks 8, 16 and 24.