Tigulixostat (IBI128) vs Febuxostat in Gout

Inclusion criteria

Participants must meet all of the following criteria to be eligible for the study:

• Age ≥ 18 years, male or female.
• Body mass index (BMI) between 18 and 40 kg/m².
• Diagnosed with gout according to the 2015 ACR/EULAR classification criteria.
• Serum uric acid (sUA) at screening:

≥ 480 μmol/L for subjects without comorbidities;

≥ 420 μmol/L for subjects with at least one concurrent condition (e.g., ≥ 2 gout attacks/year, tophi, chronic gouty arthritis, hypertension, diabetes, dyslipidemia, age of onset < 40 years).

• Voluntarily sign the informed consent form and agree to strictly follow the protocol requirements.

Exclusion criteria

Participants who meet any of the following criteria will be excluded from the study:

• History of allergy or intolerance to any component of febuxostat or Tigulixostat, or previous evidence of poor response to febuxostat treatment (e.g., sUA > 420 μmol/L after ≥ 6 weeks of febuxostat ≥ 40 mg).
• Acute gout attack within 4 weeks prior to screening or from screening to first dose.
• Use of uric acid-lowering drugs (e.g., allopurinol, febuxostat, probenecid, benzbromarone, dotinurad, recombinant uricase; excluding sodium bicarbonate) within 2 weeks before screening.
• Hyperuricemia caused by secondary gout (e.g., myeloproliferative disease, tumor, organ transplantation, enzyme deficiency, renal tubular dysfunction, lead poisoning, psoriasis, medications), excluding hyperuricemia due to renal insufficiency.
• Use of the following medications or therapies prior to screening or planned during the study:

(1)Prior urate oxidase treatment; (2)Concomitant medications affecting uric acid levels within 4 weeks before screening with dose adjustments (e.g., losartan, calcium channel blockers, diuretics, fenofibrate, atorvastatin, α-glucosidase inhibitors, insulin sensitizers, DPP4 inhibitors, SGLT2 inhibitors, metformin, GLP-1 receptor agonists, pyrazinamide, aspirin); (3)Long-term drugs dependent on xanthine oxidase metabolism (e.g., azathioprine, mercaptopurine); (4)Oral corticosteroids ≥ 10 consecutive days, or intramuscular/intravenous/intra-articular corticosteroid injection within 4 weeks before screening; (5)Biologics (e.g., TNF-α inhibitors, IL-1 inhibitors, IL-6 inhibitors) within 12 weeks before screening.

• History or evidence of any of the following diseases:

• Xanthinuria, Lech-Nyhan syndrome, 5-phosphoribosyl-1-pyrophosphate synthetase superactivity, congenital myogenic hyperuricemia, rhabdomyolysis;
• Uncontrolled severe pain not caused by gout;
• Cardiovascular events or conditions within 6 months (e.g., acute MI, ACS, unstable angina, CABG, PCI, TIA, cerebrovascular accident, severe arrhythmia, NYHA class III/IV heart failure);
• QTcF ≥ 480 ms or history of prolonged QTc interval;
• Poorly controlled hypertension (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg) or recent adjustment of antihypertensive drugs;
• Poorly controlled diabetes (HbA1c ≥ 9.0%);
• Autoimmune or inflammatory diseases requiring systemic immunosuppressive treatment;
• Active peptic ulcer or GI bleeding within 1 month;
• Diseases affecting drug absorption (e.g., IBS, IBD);
• Active hepatitis B, C, HIV, or syphilis infection;
• Active or untreated malignancy within 5 years, except specified low-risk cancers;
• Thyroid dysfunction requiring treatment. 7. Laboratory abnormalities:

(1)total bilirubin > 2×ULN, ALT or AST > 3×ULN; (2)eGFR < 30 mL/min/1.73 m². 8. Pregnant or lactating women, or participants unwilling to use effective contraception during the study and for 8 weeks after study end.

• History of alcohol or drug abuse (weekly alcohol > 21 units for males, > 14 units for females).

• Blood donation or loss ≥ 400 mL within 3 months, or prior blood transfusion.

• Participation in another interventional clinical trial within 3 months or 5 half-lives of prior investigational drug.

• Major surgery within 3 months, incomplete recovery, or planned major surgery during study.

• Presence of mental illness deemed inappropriate for study participation by the investigator.

• Any other condition judged by the investigator to potentially affect study efficacy or safety evaluation.