Tigulixostat for Gout

(EURELIA1 Trial)

No longer recruiting at 55 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Tigulixostat for people with gout, a condition that causes painful joint inflammation due to high uric acid levels. Researchers aim to evaluate the effectiveness of three different doses of Tigulixostat over six months compared to a placebo. The trial targets individuals with a history of gout and high uric acid levels, whether they are on or off other uric acid-lowering treatments. Those with frequent flare-ups who meet these conditions might find this trial suitable. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to the development of a potentially new treatment option for gout.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Tigulixostat is generally well-tolerated by patients. In previous studies, the number of gout flare-ups needing extra treatment ranged from 9.4% to 13.2% for both those taking Tigulixostat and those taking a placebo, indicating a similar effect on flare-ups. However, about 50% of patients reported some side effects. These studies suggest that Tigulixostat can be safe, as no serious side effects were found. The trial is in an advanced stage, indicating existing evidence supports its safety. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for gout?

Researchers are excited about Tigulixostat for treating gout because it introduces a novel approach by targeting the xanthine oxidase enzyme. Unlike standard treatments like allopurinol and febuxostat, which also inhibit this enzyme, Tigulixostat offers a potentially improved safety profile and efficacy. This new drug is being tested in varying doses, allowing for tailored treatments and possibly fewer side effects, which could be a game-changer for those struggling with managing gout.

What evidence suggests that Tigulixostat might be an effective treatment for gout?

Studies have shown that Tigulixostat effectively lowers uric acid levels in the blood, which is crucial for treating gout. Research indicates that Tigulixostat blocks an enzyme involved in uric acid production. In earlier studies, patients taking Tigulixostat experienced fewer gout attacks and were more likely to achieve their uric acid goals. Compared to allopurinol, a common gout medication, Tigulixostat not only lowered uric acid levels more effectively but also improved kidney health. In this trial, participants will receive different dosages of Tigulixostat or a placebo to further evaluate its effectiveness and safety. These findings suggest that Tigulixostat could be a promising option for managing gout in patients with high uric acid levels. ^{2 3 5 6 7}

Who Is on the Research Team?

Hyungjin Cho, MD

Principal Investigator

LG Chem

Are You a Good Fit for This Trial?

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

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.

I have high uric acid levels and gout according to ACR/EULAR 2015.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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]

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]

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]

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 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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05586971

NCT05586971 | Tigulixostat, Phase 3 Study, Allopurinol ... 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 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36649008/

Serum Urate-Lowering Efficacy and Safety of Tigulixostat in ... The rate of gout flares requiring rescue treatment ranged from 9.4% to 13.2% in the tigulixostat and placebo groups. The incidence of adverse events was 50.0% ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11705990/

Tigulixostat Alleviates Hyperuricemic Nephropathy by ... In this study, we discovered that Tigulixostat (LC350189) more effectively reduced SUA levels and resulted in better renal outcomes compared to allopurinol.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1551714425000370

Evaluation of the efficacy and safety of a novel xanthine ... Tigulixostat is a novel non-purine selective xanthine oxidase inhibitor for gout with hyperuricemia which has demonstrated potent in vitro and in vivo urate ...

5. prnewswire.com prnewswire.com/news-releases/innovent-announces-phase-2-results-of-tigulixostat-ibi128-xoi-in-gout-patients-were-published-at-the-27th-asia-pacific-league-of-associations-for-rheumatology-congress-302548517.html

Innovent Announces Phase 2 Results of Tigulixostat ... The collective data demonstrate that tigulixostat significantly reduces serum uric acid levels and improves urate-lowering target achievement ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05586971

NCT05586971 | Tigulixostat, Phase 3 Study, Allopurinol ... 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 ...

7. the-rheumatologist.org the-rheumatologist.org/article/tigulixostat-promising-for-patients-with-gout-hyperuricemia/

Tigulixostat Promising for Patients with Gout & ... At all three doses studied, tigulixostat significantly lowered the serum urate levels of patients with gout and hyperuricemia more than placebo.