Gout
Conditions
Brief summary
The primary purpose of this study is to compare the efficacy of Tigulixostat (IBI128) versus Febuxostat on the proportion of Chinese adults with gout achieving a serum uric acid (sUA) level \< 360 μmol/L at Week 24. The study also evaluates safety, gout attacks, kidney function, inflammation, and quality of life over 52 weeks of treatment. Approximately 600 eligible participants will be randomized to receive either Tigulixostat or Febuxostat.
Interventions
DRUGFebuxostat
Participants in this group receive Febuxostat tablets together with dummy tablets matching Tigulixostat once daily during the 24-week core treatment period. Thereafter, participants switch to Tigulixostat tablets alone once daily during the 28-week extension treatment period.
DRUGTigulixostat
Participants in this group receive Tigulixostat (IBI128) tablets together with dummy tablets matching Febuxostat once daily during the 24-week core treatment period, with dose escalation per protocol. Thereafter, participants continue Tigulixostat tablets alone once daily during the 28-week extension treatment period.
Sponsors
Innovent Biologics Technology Limited (Shanghai R&D Center)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants must meet all of the following criteria to be eligible for the study: 1. Age ≥ 18 years, male or female. 2. Body mass index (BMI) between 18 and 40 kg/m². 3. Diagnosed with gout according to the 2015 ACR/EULAR classification criteria. 4. 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). 5. 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: 1. 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). 2. Acute gout attack within 4 weeks prior to screening or from screening to first dose. 3. Use of uric acid-lowering drugs (e.g., allopurinol, febuxostat, probenecid, benzbromarone, dotinurad, recombinant uricase; excluding sodium bicarbonate) within 2 weeks before screening. 4. 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. 5. 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. 6\. History or evidence of any of the following diseases: 1. Xanthinuria, Lech-Nyhan syndrome, 5-phosphoribosyl-1-pyrophosphate synthetase superactivity, congenital myogenic hyperuricemia, rhabdomyolysis; 2. Uncontrolled severe pain not caused by gout; 3. 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); 4. QTcF ≥ 480 ms or history of prolonged QTc interval; 5. Poorly controlled hypertension (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg) or recent adjustment of antihypertensive drugs; 6. Poorly controlled diabetes (HbA1c ≥ 9.0%); 7. Autoimmune or inflammatory diseases requiring systemic immunosuppressive treatment; 8. Active peptic ulcer or GI bleeding within 1 month; 9. Diseases affecting drug absorption (e.g., IBS, IBD); 10. Active hepatitis B, C, HIV, or syphilis infection; 11. Active or untreated malignancy within 5 years, except specified low-risk cancers; 12. 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. 9\. History of alcohol or drug abuse (weekly alcohol \> 21 units for males, \> 14 units for females). 10\. Blood donation or loss ≥ 400 mL within 3 months, or prior blood transfusion. 11\. Participation in another interventional clinical trial within 3 months or 5 half-lives of prior investigational drug. 12\. Major surgery within 3 months, incomplete recovery, or planned major surgery during study. 13\. Presence of mental illness deemed inappropriate for study participation by the investigator. 14\. Any other condition judged by the investigator to potentially affect study efficacy or safety evaluation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Achieving Serum Uric Acid <360 μmol/L at Week 24 | At Week 24 | Percentage of participants with serum uric acid (sUA) level below 360 μmol/L at Week 24 after randomized treatment with Tigulixostat (IBI128) or Febuxostat in Chinese participants with gout. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Renal Function Parameters | At Week 12, 24, and 52 | Change from baseline in estimated glomerular filtration rate (eGFR) at Weeks 12, 24, and 52. |
| Change From Baseline in Inflammatory and Deposition-Related Parameters | At Weeks 12, 24, and 52 | Change from baseline in urolithiasis status, gouty tophi, and systemic inflammation as assessed by high-sensitivity C-reactive protein (hs-CRP) at Weeks 12, 24, and 52. |
| Proportion of Participants Achieving Serum Uric Acid <360 μmol/L at Week 12 | At Week 12 | Percentage of participants with serum uric acid (sUA) level below 360 μmol/L at Week 12. |
| Proportion of Participants with Serum Uric Acid <360 μmol/L at Each Scheduled Visit | At Week 0, 2, 4, 8, 12, 16, 20, 24, 32, 42, and 52 | Proportion of participants achieving a serum uric acid (sUA) level \<360 μmol/L at each scheduled visit during the 52-week study period. |
| Proportion of Participants Achieving Serum Uric Acid <300 μmol/L at Each Scheduled Visit | At Week 0, 2, 4, 8, 12, 16, 20, 24, 32, 42, and 52 | Percentage of participants with serum uric acid (sUA) level below 300 μmol/L at each scheduled visit during the 52-week treatment period. |
| Proportion of Participants Achieving Serum Uric Acid <240 μmol/L at Each Scheduled Visit | At Week 0, 2, 4, 8, 12, 16, 20, 24, 32, 42, and 52 | Percentage of participants with serum uric acid (sUA) level below 240 μmol/L at each scheduled visit during the 52-week treatment period. |
| Mean Change From Baseline in Serum Uric Acid Level at Each Scheduled Visit | At Week 0, 2, 4, 8, 12, 16, 20, 24, 32, 42, and 52 | Mean change from baseline in serum uric acid (sUA) level at each scheduled visit during the 52-week treatment period. |
| Mean Percent Change From Baseline in Serum Uric Acid Level at Each Scheduled Visit | At Week 0, 2, 4, 8, 12, 16, 20, 24, 32, 42, and 52 | Mean percent change from baseline in serum uric acid (sUA) level at each scheduled visit the 52-week treatment period. |
| Proportion and Number of Gout Flares per Participant | Every 4 weeks from first dose through Week 52 | Proportion of participants experiencing gout flares and the number of gout flares per participant during each 4-week interval following initiation of study treatment. |
| Number of Participants with Adverse Events (AEs)/Serious Adverse Events (SAEs) | Baseline through Week 54 (end of safety follow-up) | Percentage of participants who have experienced AEs/SAEs. |
Countries
China
Outcome results
None listed