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

Background: Anti-IL-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 patients with uncontrolled CRSwNP remains unclear.

Objectives: We evaluated the safety and efficacy of GR1802, a novel anti-IL-4Rα monoclonal antibody, in patients with uncontrolled CRSwNP.

Methods: Seventy patients with uncontrolled CRSwNP were randomized (1:1) to receive either GR1802 (300 mg with an initial doubled dose) or placebo every 2 weeks. Primary end points were the changes from baseline in nasal polyp score and nasal congestion score at week 16. Secondary end points 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 non-ECRSwNP subgroups. Safety was evaluated throughout the study.

Results: In uncontrolled CRSwNP participants, GR1802 significantly improved nasal polyp score and nasal congestion score compared with placebo, with least squares mean differences of -2.1 (95% confidence interval, -2.6, -1.5) and -0.8 (95% confidence interval, -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 quality of life in both ECRSwNP and non-ECRSwNP participants, as evidenced by changes in nasal polyp score, University of Pennsylvania Smell Identification Test score, and Lund-Mackay score. Treatment-related adverse events occurred in 19.4% of the GR1802 group and 17.6% of the placebo group.

Conclusion: GR1802 is well tolerated and effective in treating the overall population with uncontrolled CRSwNP.