AERIFY-1/-2: 2 phase 3 randomised controlled trials of itepekimab in former smokers with moderate-to-severe COPD

BackgroundAccumulating data implicate interleukin (IL)-33, a proinflammatory cytokine released locally upon epithelial cell damage, in the pathogenesis of chronic obstructive pulmonary disease (COPD). In a phase 2 study, itepekimab, a human monoclonal antibody against IL-33, reduced exacerbations and improved lung function in a subgroup analysis of former smokers with COPD with an acceptable safety profile.MethodsThe study designs of AERIFY-1 and AERIFY-2 are described in this article.Results and conclusion:The primary objective of AERIFY-1/2 (NCT04701983/NCT04751487), two phase 3 randomized, double-blind, placebo-controlled trials, is to assess the efficacy and safety of itepekimabversusplacebo in a population of former smokers with moderate-to-severe COPD over up to 52 weeks. An additional secondary population of current smokers are being enrolled in AERIFY-2. These two studies will enrol patients (aged 40–85 years) with COPD and chronic bronchitis who had ≥2 moderate or ≥1 severe exacerbations within the previous year despite standard-of-care triple or double background therapy. All participants are required to have ≥10-pack year smoking history, and ≥6 months since smoking cessation for former smokers. The primary endpoint is the annualized rate of moderate or severe acute exacerbation of COPD. Secondary endpoints include change from baseline in pre- and post-bronchodilator FEV1, and annualized frequency of severe exacerbations. Symptomatic endpoints include Evaluating Respiratory Symptoms in COPD, and St. George's Respiratory Questionnaire, safety and anti-drug antibody responses.