Tigulixostat for Gout

(EURELIA2 Trial)

Recruiting at 125 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 attack, 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: 12 months

2542 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing Tigulixostat, a new medication, to see if it can help people with gout by lowering high levels of uric acid in their blood. The study focuses on gout patients who have high uric acid levels, which can lead to painful attacks. By reducing uric acid, Tigulixostat aims to prevent these painful episodes.

Do I have to stop taking my current medications for the trial?

Yes, if you are currently on urate-lowering therapies (ULT), you will need to stop and undergo a washout period before participating in the study.

What data supports the idea that Tigulixostat for Gout is an effective drug?

The available research shows that Tigulixostat is effective in lowering serum urate levels in patients with gout. This is important because high levels of urate can lead to gout attacks. In a study, Tigulixostat was tested in a controlled environment where neither the patients nor the researchers knew who was receiving the actual drug or a placebo (a fake treatment). The results showed that Tigulixostat successfully reduced urate levels in patients, indicating its effectiveness as a treatment for gout. ^{1 2 3 4 5}

What safety data is available for Tigulixostat in treating gout?

The provided research does not contain specific safety data for Tigulixostat or its other names related to gout treatment. The studies focus on other drugs like tocilizumab and TNF inhibitors for rheumatoid arthritis, discussing their safety profiles and adverse events. Therefore, no relevant safety data for Tigulixostat is available in the given research. ^{6 7 8 9 10}

Is Tigulixostat a promising drug for treating gout?

Yes, Tigulixostat is a promising drug for treating gout because it effectively lowers uric acid levels in patients, which is important for managing gout. ^{1 4 5 11 12}

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 have a BMI ≤50 kg/m^2, kidney function (eGFR) ≥30 mL/min/1.73 m^2, and sUA level ≥6 mg/dL if on urate-lowering therapy or ≥7 mg/dL without it after washout. Excluded are those with xanthinuria, recent acute gout attacks, secondary hyperuricemia, enzymatic defects, or unstable medication affecting sUA.

Inclusion Criteria

Are you a Male or Female 18 - 85 years of age?

Have you been diagnosed with GOUT?

Exclusion Criteria

Have you received any oral steroids in the last 2 weeks?

Are you currently pregnant or planning a pregnancy?

I do not have uncontrolled pain unrelated to gout.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tigulixostat or Allopurinol or Placebo for up to 12 months

12 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Allopurinol
• Placebo
• Tigulixostat

Trial Overview This study tests the effectiveness and safety of three doses of Tigulixostat compared to Allopurinol and placebo in managing gout over 12 months. It's randomized, double-blind (neither doctors nor patients know who gets which treatment), multi-regional with parallel groups.

Participant Groups

Group I: Tigulixostat 300mg Experimental Treatment 1 Intervention

Tigulixostat 300mg (100mg + 200mg), Once a day (QD) for up to 12 months

Group II: Tigulixostat 200mg Experimental Treatment 1 Intervention

Tigulixostat 200mg, Once a day (QD) for up to 12 months

Group III: Tigulixostat 100mg Experimental Treatment 1 Intervention

Tigulixostat 100mg, Once a day (QD) for up to 12 months

Group IV: Titrated allopurinol (100-800mg) Active Control 1 Intervention

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.

Group V: Placebo Placebo Group 1 Intervention

Placebo, three times a day (TID) 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]

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 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]

The German biologics register RABBIT and European data show that TNF inhibitors do not increase the overall risk of cancer and are associated with a lower frequency of venous thromboembolism compared to conventional DMARDs.

Tocilizumab, an interleukin-6 inhibitor, is linked to a higher incidence of lower intestinal tract perforations, while Janus kinase inhibitors raise the risk of herpes zoster, highlighting the need for careful monitoring of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Risk profile of disease-modifying antirheumatic drugs: an update from the RABBIT register]. Albrecht, K., Strangfeld, A.[2021]

Tocilizumab, an anti-IL-6 receptor antibody, effectively improves symptoms and slows the progression of refractory rheumatoid arthritis when administered at 8 mg/kg monthly.

While there is a slightly higher incidence of nonsevere infections compared to traditional treatments, no specific infections or prolonged infections have been linked to tocilizumab, indicating it has a satisfactory safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab for the treatment of rheumatoid arthritis. Mima, T., Nishimoto, N.[2010]

Tocilizumab, an interleukin-6 receptor antagonist, has shown significant clinical improvements in rheumatoid arthritis patients at doses greater than 4 mg/kg, with the most effective dose being 8 mg/kg, which also reduces joint damage as seen in radiographic measures.

While tocilizumab is effective, it is associated with common adverse effects such as liver function abnormalities, infections, and neutropenia, highlighting the need for further research to better understand its safety profile and optimal use in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab: an interleukin-6 receptor inhibitor for the treatment of rheumatoid arthritis. Plushner, SL.[2016]

A total of 1,403,273 adverse events related to five TNF inhibitors were reported, with the most common adverse reactions including infections, musculoskeletal disorders, and gastrointestinal issues, highlighting the need for careful monitoring of patients on these medications.

Infliximab was associated with a higher rate of infusion-related reactions, while golimumab had the highest reports of lower respiratory tract infections, suggesting that different TNF inhibitors may carry unique risks that should be considered when prescribing them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristic analysis of adverse reactions of five anti-TNFɑ agents: a descriptive analysis from WHO-VigiAccess. Li, M., You, R., Su, Y., et al.[2023]

Tocilizumab, when used in combination with methotrexate (MTX) for treating rheumatoid arthritis (RA), is associated with a statistically significant increased risk of adverse events (AEs), particularly at the 8 mg/kg dosage, with an odds ratio of 1.53 compared to controls.

While there is a higher risk of infections in patients receiving the 8 mg/kg combination therapy (odds ratio of 1.30), the study found no increased incidence of malignancy, tuberculosis reactivation, or hepatitis, indicating a specific safety profile that requires monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of adverse events including serious infections in rheumatoid arthritis patients treated with tocilizumab: a systematic literature review and meta-analysis of randomized controlled trials. Campbell, L., Chen, C., Bhagat, SS., et al.[2022]

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]

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]

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

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

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. England pubmed.ncbi.nlm.nih.gov

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

6. Germany pubmed.ncbi.nlm.nih.gov

[Risk profile of disease-modifying antirheumatic drugs: an update from the RABBIT register]. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Tocilizumab for the treatment of rheumatoid arthritis. [2010]

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

Tocilizumab: an interleukin-6 receptor inhibitor for the treatment of rheumatoid arthritis. [2016]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Characteristic analysis of adverse reactions of five anti-TNFɑ agents: a descriptive analysis from WHO-VigiAccess. [2023]

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

Risk of adverse events including serious infections in rheumatoid arthritis patients treated with tocilizumab: a systematic literature review and meta-analysis of randomized controlled trials. [2022]

11. England pubmed.ncbi.nlm.nih.gov

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

12. France pubmed.ncbi.nlm.nih.gov

[Treatment of gout]. [2019]