ALIENTO and ARNASA: Study designs of two randomised, double-blind, placebo-controlled trials of astegolimab in patients with COPD

Rationale: The interleukin (IL)-33/ST2 pathway is linked to COPD exacerbations. Astegolimab, a human IgG2 monoclonal antibody, inhibits the IL-33 receptor ST2, is well tolerated and may reduce COPD exacerbations. Here, we report the study designs of the Phase IIb ALIENTO (NCT05037929) and Phase III ARNASA (NCT05595642) trials investigating the efficacy and safety of astegolimab in patients with COPD. Methods: ALIENTO and ARNASA are randomised, double-blind, placebo-controlled multicentre trials. In each trial, ~1290 patients will be enrolled and randomised (1:1:1) to receive astegolimab every 2 or every 4 weeks or placebo. Both trials will consist of a 52-week placebo-controlled period, followed by a 12-week safety follow-up period for patients who do not enter the OLE. Eligible patients must be aged 40–90 (ALIENTO) or 40–80 (ARNASA) years, former or current smokers, have a COPD diagnosis ≥12 months prior to screening and have experienced ≥2 moderate or severe exacerbations within 12 months prior to screening. Patients must have post-bronchodilator percent predicted FEV₁ ≥20‒<80% and FEV₁/FVC <0.7 at screening (ALIENTO) or at Visit 1 or 2 (ARNASA). The primary endpoint for both trials is the annualised rate of moderate and severe COPD exacerbations from baseline to Week 52. Secondary endpoints include: time to first moderate or severe COPD exacerbation; patient-reported outcomes (St. George9s Respiratory Questionnaire-COPD, Evaluating Respiratory Symptoms in COPD); and change from baseline in post-bronchodilator FEV₁ at Week 52. Conclusions: ALIENTO and ARNASA aim to establish the efficacy and safety of astegolimab in the treatment of patients with COPD.