Objective: To evaluate the efficacy and safety of Firsekibart, a fully human anti-IL-1β monoclonal antibody, in patients with acute gouty arthritis (GA) who are contraindicated for, intolerant of, or unresponsive to NSAIDs and/or colchicine. Methods: In this phase III trial conducted from 2022 to 2024, 313 patients aged 18-75 years, meeting the 2015 ACR preliminary criteria for acute primary gout and with ≥2 episodes in the preceding year, were randomized 1:1 to receive a single subcutaneous dose of Firsekibart (200 mg) or an intramuscular dose of Compound betamethasone (CB) 7 mg. The trial included a 48-week treatment period (24 weeks double-blind and 24 weeks open-label). Co-primary endpoints were the change in pain intensity from baseline to 72 hours in the most affected joint (measured on a VAS scale) and the time to the first new episode over 12 weeks. Results: Firsekibart demonstrated non-inferiority in pain reduction at 72 hours compared to CB (-57.09 mm vs. -53.77 mm, Least Squares Mean). Additionally, Firsekibart significantly reduced the risk of new flares by 90% over 12 weeks (HR= 0.10; 95% CI: 0.06, 0.17; p<0.0001), by 87% over 24 weeks (HR=0.13; 95% CI: 0.08, 0.21; p<0.0001) and by 70% over 48 weeks (HR=0.30; 95%CI: 0.22,0.41; p<0.0001). The proportion of patients experiencing at least one new flare was significantly lower with Firsekibart compared to CB at 12 weeks (10.9% vs 65.2%), 24 weeks (14.7% vs 66.5%) and 48 weeks (44.9% vs 74.8 %). The mean number of new flares per patient was also significantly lower in the Firsekibart group over both 12 weeks (0.2 ± 0.52 vs 1.2 ± 1.27), 24 weeks (0.2 ± 0.79 vs 1.6 ± 1.79) and 48 weeks (0.7+1.25 vs 2.0+1.94). The total number of adverse events and treatment-related adverse events was lower in the Firsekibart group (365 and 146, respectively) compared to the CB group (471 and 188, respectively). Treatment-related serious adverse events were reported only in the CB-treated group (3 patients). Conclusion: Firsekibart provides non-inferior short-term pain relief and significantly better prevention of new flares compared to CB, with an improved safety profile in patients with acute gouty arthritis. These findings support the potential of Firsekibart as a valuable alternative therapy for patients with acute gouty arthritis.