Tigulixostat for Gout

(EURELIA2 Trial)

No longer recruiting at 317 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a new treatment, Tigulixostat, for individuals with gout, a condition causing painful joint inflammation due to high uric acid levels. Researchers compare three doses of Tigulixostat with a commonly used gout medication, allopurinol, and a placebo. The trial welcomes participants with a history of gout and high uric acid levels (hyperuricemia), whether they are currently on or off urate-lowering therapies. Participants should not have experienced a recent intense gout attack or have certain other medical conditions. As a Phase 3 trial, this study is the final step before FDA approval, allowing participants to contribute to the potential availability of a new gout treatment.

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.

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

Research has shown that Tigulixostat underwent safety testing in earlier studies. In these studies, 9.4% to 13.2% of patients experienced gout flare-ups requiring additional treatment, similar to the placebo group. About half of the patients taking Tigulixostat reported side effects, though not all were serious.

The treatment significantly lowered uric acid levels in gout patients, indicating its effectiveness. While these studies offer some reassurance about its safety, Tigulixostat's progression to a phase 3 trial suggests it was safe enough in earlier phases for testing on a larger population. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Tigulixostat for gout because it offers a potentially new approach to managing this painful condition. Unlike traditional treatments like allopurinol, which primarily focus on lowering uric acid levels, Tigulixostat is designed to target and inhibit a specific enzyme that plays a role in uric acid production. This novel mechanism of action could provide more effective control of uric acid levels with potentially fewer side effects. Additionally, Tigulixostat is administered once daily, which may improve patient adherence compared to some current treatments that require multiple daily doses.

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

Research has shown that Tigulixostat, which participants in this trial may receive, holds promise for treating gout. Studies have found it effectively lowers uric acid levels in the blood, crucial for managing gout. One study discovered that Tigulixostat reduced uric acid more effectively than allopurinol, another treatment option in this trial. Additionally, Tigulixostat demonstrated better results for kidney health in people with high uric acid levels. Early data also suggest it meets uric acid-lowering goals effectively. This makes Tigulixostat a strong option for treating gout 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 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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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]

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]

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]

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]

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]

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]

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]

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]

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.