Tigulixostat for Gout

(EURELIA1 Trial)

Recruiting at 37 trial locations

Overseen By Younghwan Jang

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: LG Chem

Must be taking: Urate-lowering therapies

Must not be taking: Pegloticase

Disqualifiers: Secondary hyperuricemia, Acute gout, Xanthinuria, Rheumatoid arthritis, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

350 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing Tigulixostat, a medication that may help people with gout by lowering high uric acid levels. The study focuses on gout patients who have too much uric acid in their blood. By reducing uric acid, Tigulixostat aims to prevent or lessen painful gout attacks.

Will I have to stop taking my current medications?

If you are currently on urate-lowering therapies, you will need to stop taking them for a washout period (time without taking certain medications) before participating in the study.

What data supports the effectiveness of the drug Tigulixostat for treating gout?

Research shows that Tigulixostat, a nonpurine xanthine oxidase inhibitor, effectively lowers serum urate levels in gout patients with high uric acid, which is a key factor in managing gout. ^{1 2 3 4 5}

What safety data exists for Tigulixostat in humans?

A study on Tigulixostat for gout patients with high uric acid levels found it to be generally safe, as it was tested in a controlled environment comparing it to a placebo (a dummy treatment). ^{1 4 6 7 8}

What makes the drug Tigulixostat unique for treating gout?

Tigulixostat is unique because it is a nonpurine xanthine oxidase inhibitor, which means it lowers uric acid levels in the blood by blocking an enzyme involved in uric acid production, offering a different mechanism compared to traditional treatments like allopurinol. ^{1 3 4 9 10}

Research Team

Jisoo Lee, MD

Principal Investigator

LG Chem

Eligibility Criteria

Adults aged 18-85 with gout and high uric acid levels are eligible for this trial. They must meet specific criteria for hyperuricemia, have a BMI ≤50 kg/m2, and an eGFR ≥30 mL/min/1.73 m2. Those on urate-lowering therapies need to reach certain uric acid levels after washout to participate.

Inclusion Criteria

I am between 18 and 85 years old.

My uric acid levels are high despite taking or not taking urate-lowering medication.

My uric acid levels are high, even with or without gout medication.

Exclusion Criteria

I have taken pegloticase for gout that didn't improve with standard treatments.

I have had a severe gout attack in the last 2 weeks.

I haven't taken drugs that change uric acid levels in the last 3 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tigulixostat or placebo once a day for up to 6 months

6 months

Monthly visits for efficacy and safety assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• Tigulixostat

Trial Overview The study is testing the effectiveness and safety of Tigulixostat at three different doses compared to a placebo in treating gout patients over six months. Participants will be randomly assigned to either the medication or placebo group.

Participant Groups

Group I: Tigulixostat 300mg Experimental Treatment 1 Intervention

Tigulixostat 300mg (100mg + 200mg), Once a day (QD) for up to 6 months

Group II: Tigulixostat 200mg Experimental Treatment 1 Intervention

Tigulixostat 200mg, Once a day (QD) for up to 6 months

Group III: Tigulixostat 100mg Experimental Treatment 1 Intervention

Tigulixostat 100mg, Once a day (QD) for up to 6 months

Group IV: Placebo Placebo Group 1 Intervention

Placebo, Once a day (QD) for up to 6 months

Who Is Running the Clinical Trial?

LG Chem

Lead Sponsor

Trials

66

Recruited

33,800+

Shin Hak-Cheol

LG Chem

Chief Executive Officer since 2022

Bachelor's degree in Mechanical Engineering from Seoul National University

Ko Yoon-joo

LG Chem

Chief Medical Officer

MD from Yonsei University

Findings from Research

In a phase II trial involving 143 gout patients, tigulixostat significantly lowered serum urate levels, achieving the target level of <5.0 mg/dl in 47.1% to 62.2% of patients across different doses, compared to only 2.9% in the placebo group.

The treatment was well-tolerated, with adverse events being mostly mild to moderate, and the rate of gout flares was similar between tigulixostat and placebo groups, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum Urate-Lowering Efficacy and Safety of Tigulixostat in Gout Patients With Hyperuricemia: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Trial. Terkeltaub, R., Lee, J., Min, J., et al.[2023]

In a phase III study involving 1315 adults with gout, weekly subcutaneous rilonacept 160 mg significantly reduced the frequency of gout flares by 70.3% compared to placebo, demonstrating its efficacy in preventing gout attacks.

The safety profile of rilonacept was consistent with previous studies, with no new safety concerns identified; however, there were more injection site reactions and slightly higher withdrawal rates due to adverse events compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rilonacept for gout flare prevention in patients receiving uric acid-lowering therapy: results of RESURGE, a phase III, international safety study. Sundy, JS., Schumacher, HR., Kivitz, A., et al.[2019]

From 2007 to 2011, there was a notable increase in gout diagnoses during visits to healthcare providers, particularly after the introduction of febuxostat in 2009, although the overall percentage of visits for gout remained low at about 1.2%.

Despite the introduction of febuxostat, treatment trends for gout did not significantly change during the study period, indicating that this new medication had little impact on the overall management of gout in the US by 2011.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of gout visits in the United States for the years 2007 to 2011. Castro, KE., Corey, KD., Raymond, DL., et al.[2022]

In a 3-month study involving 1,790 patients with gout, both extended release (XR) and immediate release (IR) formulations of febuxostat significantly reduced serum urate levels to below 5.0 mg/dl compared to placebo, demonstrating their efficacy in managing gout.

Both febuxostat formulations were well tolerated across all renal function subgroups, including those with severe renal impairment, with low rates of adverse events and no significant difference in gout flare rates among treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Febuxostat Extended and Immediate Release in Patients With Gout and Renal Impairment: A Phase III Placebo-Controlled Study. Saag, KG., Becker, MA., Whelton, A., et al.[2020]

In a study of 678 gout patients treated with febuxostat, higher adherence to the medication and lower baseline serum uric acid (sUA) levels were identified as key factors for achieving the treatment goal of sUA <6 mg/dL.

The research highlights that patients who remained on febuxostat longer and had better adherence were more likely to reach the target sUA levels, suggesting that encouraging adherence could improve treatment outcomes for gout patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of reaching a serum uric acid goal in patients with gout and treated with febuxostat. Sheer, R., Null, KD., Szymanski, KA., et al.[2020]

In a phase IIIB study involving 109 gout patients, febuxostat (80 mg QD) significantly reduced serum urate levels more effectively than allopurinol (300 mg QD) over 12 weeks, with a decrease of over 40% compared to approximately 30% for allopurinol.

Both treatments had similar safety profiles, with no serious skin reactions reported, making febuxostat a suitable option for Han Chinese patients with gout who are HLA-B*5801 negative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of oral febuxostat for treatment of HLA-B*5801-negative gout: a randomized, open-label, multicentre, allopurinol-controlled study. Yu, KH., Lai, JH., Hsu, PN., et al.[2022]

Febuxostat effectively lowers uric acid levels in patients with hyperuricemia and gout, achieving a reduction of up to 48% after 104 weeks, with about 60% of patients reaching the target uric acid level of less than 6 mg/dL after 52 weeks of treatment.

While febuxostat is a promising alternative to allopurinol, it carries a risk of gout flares, with up to 70% of patients experiencing flares during the first year of therapy, even with preventive treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Febuxostat: a selective xanthine oxidase inhibitor for the treatment of hyperuricemia and gout. Bruce, SP.[2022]

Febuxostat appears to significantly reduce the incidence of serious skin reactions like Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in gout patients, indicating a potential safety benefit.

However, in gout patients with comorbidities, febuxostat is associated with an increased risk of acute myocardial infarction (AMI), percutaneous coronary intervention (PCI), and all-cause mortality, suggesting a need for careful consideration in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of febuxostat on adverse events and mortality in gout in Taiwan: An interrupted time series analysis. Tsai, PH., Kuo, CF., Liu, JR., et al.[2023]

Colchicine is the standard treatment for acute gout flares in France, with dosage adjustments needed based on renal function and age to minimize digestive toxicity.

To prevent future gout flares and reduce tophus size, maintaining uric acid levels below 60 mg/L is crucial, often requiring higher doses of allopurinol, while alternative treatments like febuxostat and uricolytic drugs are being explored for severe cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of gout]. Dubost, JJ., Mathieu, S., Soubrier, M.[2019]

Febuxostat is a selective inhibitor of xanthine oxidase, which is being developed as an oral treatment for gout, indicating its potential efficacy in managing this condition.

The drug's launch in Japan was delayed due to the need for additional clinical trials, while an application for approval in the EU was anticipated by the end of 2005.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Febuxostat (Teijin/Ipsen/TAP). Tomlinson, B.[2015]

References

1. United States pubmed.ncbi.nlm.nih.gov

Serum Urate-Lowering Efficacy and Safety of Tigulixostat in Gout Patients With Hyperuricemia: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Trial. [2023]

2. Canada pubmed.ncbi.nlm.nih.gov

Rilonacept for gout flare prevention in patients receiving uric acid-lowering therapy: results of RESURGE, a phase III, international safety study. [2019]

3. England pubmed.ncbi.nlm.nih.gov

An evaluation of gout visits in the United States for the years 2007 to 2011. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Febuxostat Extended and Immediate Release in Patients With Gout and Renal Impairment: A Phase III Placebo-Controlled Study. [2020]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Predictors of reaching a serum uric acid goal in patients with gout and treated with febuxostat. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of oral febuxostat for treatment of HLA-B*5801-negative gout: a randomized, open-label, multicentre, allopurinol-controlled study. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Febuxostat: a selective xanthine oxidase inhibitor for the treatment of hyperuricemia and gout. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Effect of febuxostat on adverse events and mortality in gout in Taiwan: An interrupted time series analysis. [2023]

9. France pubmed.ncbi.nlm.nih.gov

[Treatment of gout]. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Febuxostat (Teijin/Ipsen/TAP). [2015]