AR882 for Gout

Recruiting at 80 trial locations

Overseen By Director Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Arthrosi Therapeutics

Disqualifiers: Malignancy, Pregnant, Kidney stones, 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

750 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will assess the serum uric acid lowering effect and safety of AR882 in gout patients at two doses compared to placebo over 12 months

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that patients on urate-lowering therapy (ULT) can participate, so you may be able to continue those medications.

What safety data exists for AR882 (Arhalofenate) in humans?

Arhalofenate, also known as AR882, has been studied for safety in people with gout. It was generally well-tolerated when used with another gout medication, febuxostat, and showed a reduction in arthritis flares. ^{1 2 3 4 5}

How is the drug AR882 different from other gout treatments?

AR882, also known as arhalofenate, is unique because it not only helps lower uric acid levels in the blood but also reduces the frequency of gout flares by inhibiting inflammation through a specific pathway (AMPK signaling). This dual action sets it apart from other treatments that typically focus on just lowering uric acid. ^{2 3 4 6 7}

What data supports the effectiveness of the drug AR882 for treating gout?

Research on arhalofenate, a component of AR882, shows it can lower uric acid levels and reduce gout flares by inhibiting certain inflammatory responses. This suggests AR882 might be effective for gout by similar mechanisms. ^{3 4 8 9 10}

Research Team

Robert Keenan, MD

Principal Investigator

Arthrosi Therapeutics, Inc.

Eligibility Criteria

This trial is for individuals with gout, characterized by high uric acid levels. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and may be required to have a specific range of uric acid levels.

Inclusion Criteria

My kidney function is within the required range.

My uric acid level is above 6 mg/dL despite being on treatment.

My uric acid level is 7 mg/dL or higher and I am not on urate-lowering therapy.

Exclusion Criteria

I haven't had cancer in the last 5 years, except for skin cancer that was treated successfully.

Pregnant or breastfeeding

I have had painful kidney stones in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AR882 or placebo once daily for 12 months to assess serum uric acid lowering effect and safety

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• AR882

Trial Overview The study is testing the effectiveness and safety of AR882 in reducing serum uric acid in gout patients. Two different doses of AR882 (50 mg and 75 mg) will be compared against a placebo over the course of 12 months.

Participant Groups

Group I: AR882 75 mg Experimental Treatment 1 Intervention

AR882 75 mg taken once daily for 12 months

Group II: AR882 50 mg Experimental Treatment 1 Intervention

AR882 50 mg taken once daily for 12 months

Group III: Placebo Placebo Group 1 Intervention

AR882 matching placebo taken once daily for 12 months

Who Is Running the Clinical Trial?

Arthrosi Therapeutics

Lead Sponsor

Trials

9

Recruited

1,900+

Findings from Research

A systematic review of 68 gout trials revealed that the average number of recommended OMERACT outcome domains reported was low, with only 2.9 for acute and 2.5 for chronic gout trials, indicating a lack of adherence to established guidelines.

Key aspects such as health-related quality of life and joint damage imaging were not assessed in any of the trials, highlighting significant gaps in the evaluation of gout interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes assessed in trials of gout and accordance with OMERACT-proposed domains: a systematic literature review. Araújo, F., Cordeiro, I., Ramiro, S., et al.[2018]

Arhalofenate acid significantly reduces inflammation and acute arthritis flares in gout by inhibiting the NLRP3 inflammasome and activating AMPK, as shown in both murine models and macrophage studies.

In vivo studies demonstrated that arhalofenate treatment decreased leukocyte and neutrophil influx, as well as inflammatory cytokines, indicating its potential as an effective anti-inflammatory treatment for gout.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Arhalofenate acid inhibits monosodium urate crystal-induced inflammatory responses through activation of AMP-activated protein kinase (AMPK) signaling. McWherter, C., Choi, YJ., Serrano, RL., et al.[2019]

A study is being conducted to evaluate the effectiveness of a personalized smartphone app for self-managing gout, aiming to improve adherence to urate-lowering therapy (ULT) and achieve target serum urate levels of 0.36 mmol/L or less in patients.

The trial involves a cluster randomized design with GP practices, and it aims to show at least a 30% improvement in achieving target serum urate levels in the intervention group compared to a control group over 6 months, with a total of 6 and 12-month follow-up for various health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of an electronic patient-centred self-management tool for gout sufferers: a cluster randomised controlled trial protocol. Day, RO., Frensham, LJ., Nguyen, AD., et al.[2019]

In a phase II trial with 32 gout volunteers, the combination of arhalofenate (ARH) and febuxostat (FBX) significantly reduced serum uric acid (SUA) levels, achieving a 63% decrease with ARH 800 mg and FBX 80 mg, with all subjects reaching SUA levels below 6 mg/dl.

The combination therapy was well tolerated and safe, demonstrating complementary mechanisms of action that enhanced uric acid lowering compared to either drug alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Pharmacodynamics, Pharmacokinetics, and Safety of Arhalofenate in Combination with Febuxostat When Treating Hyperuricemia Associated with Gout. Steinberg, AS., Vince, BD., Choi, YJ., et al.[2018]

In a study of 60 patients with acute gouty arthritis, the combination of electroacupuncture, blood-letting puncture, and cupping showed a significantly higher effective rate of 96.7% compared to 86.7% for the control group receiving Probenecid.

Both treatments reduced blood uric acid levels, but the observation group had significantly lower levels post-treatment, indicating that the combined therapy may be more effective in managing gout symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Observation on therapeutic effect of electroacupuncture plus blood-letting puncture and cupping combined with diet intervention for treatment of acute gouty arthritis]. Zhao, QW., Liu, J., Qu, XD., et al.[2013]

A novel inhibitor of the hURAT1 protein, isobavachin, was identified from a natural product database, showing a strong ability to inhibit uric acid uptake with an IC50 value of 0.39 μM, comparable to the existing drug verinurad.

Isobavachin also demonstrated significant effectiveness in reducing serum uric acid levels in vivo, suggesting it could be a promising new treatment option for hyperuricemia and gout.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel natural scaffold as hURAT1 inhibitor identified by 3D-shape-based, docking-based virtual screening approach and biological evaluation. Chen, X., Zhao, Z., Luo, J., et al.[2022]

In a mouse model of acute gout, blocking the angiotensin type 2 receptor (AT2R) with the antagonist PD123319 significantly reduced pain and inflammation, showing a 44% reduction in mechanical allodynia and a 45% decrease in edema formation.

The study suggests that AT2R activation contributes to pain in gout, and its antagonism could be a promising therapeutic strategy for managing gout arthritis, as evidenced by reduced inflammatory markers and pain responses in treated mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Angiotensin type 2 receptor antagonism as a new target to manage gout. Vieira, TN., Saraiva, ALL., Guimarães, RM., 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]

Chronic hyperuricemia, the primary cause of gout, results from insufficient renal clearance of uric acid, influenced by factors like obesity, alcohol consumption, and genetics.

Effective management of gout involves diagnosing through crystal identification, gradually introducing uric acid-lowering therapies, and setting a low target for plasma urate levels to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The epidemiology and treatment of gout. McGill, NW.[2020]

In an experimental model of acute gout in rabbits, the injection of monosodium urate (MSU) crystals led to significant joint swelling and neutrophil infiltration, highlighting the role of neutrophils in acute inflammation associated with gout.

The study found that locally produced interleukin-8 (IL-8) levels increased in the synovial fluid before neutrophil infiltration, and blocking IL-8 with a neutralizing antibody reduced joint swelling and neutrophil presence, indicating IL-8's critical role in the inflammatory response in gout.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attenuation of monosodium urate crystal-induced arthritis in rabbits by a neutralizing antibody against interleukin-8. Nishimura, A., Akahoshi, T., Takahashi, M., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Outcomes assessed in trials of gout and accordance with OMERACT-proposed domains: a systematic literature review. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Arhalofenate acid inhibits monosodium urate crystal-induced inflammatory responses through activation of AMP-activated protein kinase (AMPK) signaling. [2019]

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

Effectiveness of an electronic patient-centred self-management tool for gout sufferers: a cluster randomised controlled trial protocol. [2019]

4. Canada pubmed.ncbi.nlm.nih.gov

The Pharmacodynamics, Pharmacokinetics, and Safety of Arhalofenate in Combination with Febuxostat When Treating Hyperuricemia Associated with Gout. [2018]

5. China pubmed.ncbi.nlm.nih.gov

[Observation on therapeutic effect of electroacupuncture plus blood-letting puncture and cupping combined with diet intervention for treatment of acute gouty arthritis]. [2013]

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

Novel natural scaffold as hURAT1 inhibitor identified by 3D-shape-based, docking-based virtual screening approach and biological evaluation. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Angiotensin type 2 receptor antagonism as a new target to manage gout. [2023]

8. 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]

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

The epidemiology and treatment of gout. [2020]

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

Attenuation of monosodium urate crystal-induced arthritis in rabbits by a neutralizing antibody against interleukin-8. [2019]