Tigulixostat, Phase 3 Study, Allopurinol Controlled in Gout Patients

Study Overview
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Brief Summary
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The aim of this 12-month randomized multi-regional double-blind parallel group allopurinol and placebo-controlled phase 3 study is to assess the efficacy and safety of three different doses of Tigulixostat in gout patients with hyperuricemia.

Official Title
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A Randomized, Multi-regional, Double-blind, Double-dummy Parallel-group, Placebo and Allopurinol-controlled Phase 3 Study to Assess the Efficacy and Safety of Tigulixostat in Gout Patients With Hyperuricemia

Conditions
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Gout, Hyperuricemia, Gout Flare, Tophi

Intervention / Treatment
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* Drug: Tigulixostat
* Drug: Allopurinol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects between the ages of 18 85 years, inclusive. Subjects with hyperuricemia and a history or presence of gout per American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2015 criteria. Subjects who are currently on urate-lowering therapies (ULT) with an sUA level ≥6.0 mg/dL at screening (Visit 1); or subjects who are currently not on ULT with an sUA level ≥7.0 mg/dL at screening (Visit 1). Subjects currently on ULT will undergo washout and must have an sUA level ≥7.0 mg/dL at Visit 3 to be randomized and participate in the study. Subjects with a Body Mass Index ≤50 kg/m2 and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 at screening (Visit 1). Exclusion Criteria: Subjects with secondary hyperuricemia and enzymatic defects. Subjects experiencing an acute gout attack (intense pain, swelling, or/and tenderness in the joint area) within 2 weeks prior to screening (Visit 1). Subjects who have received pegloticase to treat gout which has not responded to the usual treatments. Subjects who have not been receiving stable doses of drugs known to affect sUA levels for the last 3 weeks prior to screening (Visit 1). Subjects with a history of xanthinuria (elevated levels of xanthine in the urine).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tigulixostat 100mg<br>Tigulixostat 100mg, Once a day (QD) for up to 12 months | Drug: Tigulixostat<br>* Xanthine Oxidase Inhibitor<br>* Other names: LC350189;|
| Experimental: Tigulixostat 200mg<br>Tigulixostat 200mg, Once a day (QD) for up to 12 months | Drug: Tigulixostat<br>* Xanthine Oxidase Inhibitor<br>* Other names: LC350189;|
| Experimental: Tigulixostat 300mg<br>Tigulixostat 300mg (100mg + 200mg), Once a day (QD) for up to 12 months | Drug: Tigulixostat<br>* Xanthine Oxidase Inhibitor<br>* Other names: LC350189;|
| Active Comparator: Titrated allopurinol (100-800mg)<br>Allopurinol 100-800mg, three times a day (TID) for up to 12 months. The allopurinol dose will be increased in 100 mg increments up to 800mg. | Drug: Allopurinol<br>* Xanthine Oxidase Inhibitor<br>|
| Placebo Comparator: Placebo<br>Placebo, three times a day (TID) for up to 6 months. | Drug: Placebo<br>* Matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects with sUA levels <6.0 mg/dL sustained at months 4, 5, and 6 | Serum uric acid (sUA) level will be measured at Month 4,5, and 6 | Up to Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects with sUA levels <5.0 mg/dL sustained at months 4, 5, and 6 | Serum uric acid (sUA) level will be measured at Month 4,5, and 6 | Up to Month 6 | 
| Proportion of subjects with at least one gout flare from Month 6 to Month 12. | Gout flare (intense pain, swelling, or/and tenderness in the joint area) will be assessed from baseline up to 12 months | From Month 6 to Month 12 | 
| Proportion of subjects with complete resolution of ≥1 target tophus by Month 12 | Tophi will be measured by independent central blind reader | Up to Month 12 | 
| Incidence rate of adverse event | Safety assessment | Up to Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gout, Hyperuricemia, Xanthine Oxidase Inhibitor