Tigulixostat versus Febuxostat to lower uric acid in adults with gout

A Randomized, Double-Blind, Double-Dummy, Multi-Center, Phase III Study Comparing the Efficacy and Safety of Tigulixostat (IBI128) and Febuxostat in Chinese Subjects With Gout

This trial will try to see if tigulixostat helps Chinese adults with gout reach a target uric acid level (below 360 μmol/L) better than febuxostat.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 600 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Innovent Biologics Technology Limited (Shanghai R&D Center) (Industry-sponsored)
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07414394 on ClinicalTrials.gov

What this trial studies

This randomized Phase 3 study will enroll about 600 Chinese adults with gout and assign them to receive either tigulixostat (IBI128) or febuxostat. The primary endpoint is the proportion of participants achieving serum uric acid <360 μmol/L at Week 24, with additional safety and efficacy measures followed through 52 weeks. Secondary outcomes include frequency of gout attacks, kidney function, inflammatory markers, and quality of life. The trial is sponsored by Innovent Biologics and conducted at Fudan University Huashan Hospital in Shanghai.

Who should consider this trial

Good fit: Adults (≥18 years) with gout per 2015 ACR/EULAR criteria, BMI 18–40 kg/m², and elevated serum uric acid meeting the protocol thresholds who can give informed consent are the intended participants.

Not a fit: Patients with known allergy or intolerance to febuxostat or tigulixostat, those with prior poor response to febuxostat, or those unable to attend the Shanghai site are unlikely to receive benefit from participating.

Why it matters

Potential benefit: If successful, tigulixostat could provide a comparable or better option than febuxostat for lowering uric acid and reducing gout flares in patients.

How similar studies have performed: Other xanthine oxidase inhibitors such as febuxostat and allopurinol have a proven record of lowering serum uric acid, while tigulixostat is a newer agent with more limited phase 3 data published so far.

Eligibility criteria

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.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Fudan University HuaShan Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Chunmiao Li

Conditions Gout