Efficacy and safety of GR1802 in uncontrolled chronic rhinosinusitis with nasal polyps: Placebo-controlled phase 2 trial

Anti-interleukin-4 receptor subunit alpha (IL-4Rα) treatments can effectively treat eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). However, their impact on the overall population of uncontrolled CRSwNP remains unclear. To evaluate the safety and efficacy of GR1802, a novel anti-IL-4Rα monoclonal antibody, in uncontrolled CRSwNP patients. Seventy uncontrolled CRSwNP participants were randomized (1:1) to receive either GR1802 (300 mg with an initial doubled dose) or placebo every 2 weeks. Primary endpoints were the changes from baseline in nasal polyp score (NPS) and nasal congestion score (NCS) at week 16. Secondary endpoints mainly included change from baseline in total nasal symptom score (TNSS), 22-item Sino-Nasal Outcome Test (SNOT-22) score, and Lund-Mackay score. Efficacy (exploratory) was also analyzed in ECRSwNP and NECRSwNP subgroups. Safety was evaluated throughout the study. In uncontrolled CRSwNP participants, GR1802 significantly improved NPS and NCS when compared to placebo, with least squares (LS) mean differences of -2·1 (95% confidence interval [CI] [-2·6, -1·5]) and -0·8 (95% CI [-1·1, -0·4]) respectively. Participants treated with GR1802 had significantly decreased TNSS, SNOT-22 score, and Lund-Mackay score. The subgroup analysis demonstrated that GR1802 improved the symptoms and life quality both in ECRSwNP and NECRSwNP participants, as evidenced by changes in NPS, University of Pennsylvania Smell Identification Test (UPSIT) score, and Lund-Mackay score. Treatment-related adverse events occurred in 19·4 % of the GR1802 group and 17·6 % of the placebo group. GR1802 is well-tolerated and effective in treating the overall population with uncontrolled CRSwNP.