Gout, one of the most prevalent inflammatory arthritides worldwide, is primarily driven by interleukin-1β (IL-1β)-mediated inflammation. Despite available therapies, current treatment options have significant limitations, including contraindications, adverse effects, and suboptimal responses in certain patient populations, underscoring the urgent need for novel IL-1 inhibitors to address these unmet clinical needs. This study aimed to evaluate the safety, pharmacokinetics (PK), and efficacy of UA007, a novel recombinant human IL-1 receptor antagonist with an amino acid sequence identical to anakinra, in Chinese patients with gout.

The clinical development program comprised two sequential studies. First, a Phase I randomized, double-blind, placebo-controlled trial (ChiCTR2500097173) assessed the safety and PK profile of single-dose UA007 in 10 patients with inter-critical gout. Subsequently, a Phase IIa open-label, single-arm trial (ChiCTR2200062847) evaluated the efficacy and safety of UA007 (90 mg/day for 3 consecutive days) in 20 patients with acute gout flares. The primary efficacy endpoint was the change in Visual Analog Scale (VAS) pain score for the most affected joint at 72 hours post-initial dose compared to baseline. Secondary endpoints included frequency and intensity of gout flares, levels of inflammatory markers (CRP, IL-1β), and comprehensive safety assessments.

Phase I demonstrated favorable pharmacokinetic profiles with Cmax of 786.28 ± 244.88 ng/mL and elimination half-life of 4.99 ± 1.58 hours, with no severe adverse events (SAEs) reported. In Phase IIa, UA007 produced rapid and significant pain relief, with mean VAS reduction of –5.92 at 72 hours (95% CI: –6.65 to –5.20; p<0.001). Onset of analgesia was rapid (median pain relief achieved by 6 hours), and the effect was sustained, with 95% of patients maintaining pain control through Day 7. Consistent with its mechanism of action, UA007 markedly reduced systemic inflammation, with CRP decreasing by >80% at 72 hours. Lipid abnormalities were the most frequently observed adverse events (hypertriglyceridemia in 25% of Phase I and 15% of Phase IIa participants); all were mild and self-limiting without requiring intervention.

UA007 provides rapid, sustained analgesia and potent anti-inflammatory effects with a favorable safety and tolerability profile in Chinese patients with gout. These findings support the advancement of UA007 into Phase III clinical trials for gout management.