AR882 for Gout

Not currently recruiting at 82 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AR882 to determine if it can safely lower uric acid levels in people with gout. Gout, a form of arthritis, causes intense pain and swelling, often in the big toe. Participants will receive either a 50 mg or 75 mg dose of AR882, or a placebo, once a day for 12 months. The trial seeks individuals who have experienced at least two gout attacks in the past year and are not currently on certain medications for uric acid. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for gout.

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.

Is there any evidence suggesting that AR882 is likely to be safe for humans?

Research has shown that AR882 is generally safe and well-tolerated. In earlier studies, patients used AR882 for up to a year without encountering any serious safety problems. The most common side effect was a gout flare, occurring in about 30% of patients. No serious health issues were linked to AR882, suggesting its safety for long-term use in treating gout. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for gout?

Unlike the standard gout treatments that often focus on reducing uric acid production or increasing its excretion, AR882 is unique because it acts as a selective uric acid reabsorption inhibitor. This means it specifically targets and blocks the URAT1 transporter, which is responsible for reabsorbing uric acid in the kidneys, leading to more effective reduction of uric acid levels in the blood. Researchers are excited about AR882 because it offers a new mechanism of action that could provide better management of gout symptoms and potentially fewer side effects compared to conventional treatments like allopurinol and febuxostat. Additionally, the once-daily oral dosing of AR882 makes it a convenient option for patients.

What evidence suggests that AR882 might be an effective treatment for gout?

Research has shown that AR882 helps lower uric acid levels in people with gout. In this trial, participants will receive either AR882 at a 50 mg or 75 mg dose, or a placebo. Studies have found that AR882, especially at the 75 mg dose, reduces the amount of urate crystals, a major issue in gout. Another study suggested that AR882 works better than some current treatments and is safe to use. Specifically, patients in that study experienced relief from gout symptoms with AR882, making it a promising option for lowering uric acid levels. ^{1 2 6 7 8}

Who Is on the Research Team?

Robert Keenan, MD

Principal Investigator

Arthrosi Therapeutics, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05119686

Phase 2b Evaluation of Efficacy and Safety of AR882 in ... It identifies the role of the intervention that participants receive. Types of arms include experimental arm, active comparator arm, placebo comparator arm, ...

2. ard.bmj.com ard.bmj.com/content/82/Suppl_1/192.1

OP0295 A 12-WEEK, RANDOMIZED, DOUBLE-BLINDED ... This study suggests AR882 may offer improved efficacy with acceptable safety compared to existing therapies for gout.

3. arthrosi.com arthrosi.com/arthrosi-therapeutics-achieves-full-enrollment-of-the-second-pivotal-phase-3-trial-of-pozdeutinurad-ar882-in-patients-with-gout-including-those-with-tophaceous-gout/

Enrollment completed well ahead of schedule Arthrosi Therapeutics Achieves Full Enrollment of the Second Pivotal Phase 3 Trial of Pozdeutinurad (AR882) in Patients with Gout, Including ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06439602

Phase 3 Evaluation of Efficacy and Safety of AR882 in Gout ... 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.

5. ard.bmj.com ard.bmj.com/content/83/Suppl_1/409.2

POS0268 AR882, A NOVEL AND SELECTIVE URAT1 ... The AR882 75 mg alone or combined with allopurinol showed reduction of total urate crystal volume from baseline to Month 6 with sustained crystal volume ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0003496725013354

Annals of the Rheumatic Diseases Pozdeutinurad (AR882), a novel and selective URAT1 inhibitor, has demonstrated significant sustained reduction in serum urate (sUA), marked reduction in ...

7. acrabstracts.org acrabstracts.org/abstract/efficacy-and-safety-of-ar882-a-selective-uric-acid-transporter-1-urat1-inhibitor-in-gout-patients-with-various-baseline-characteristics-following-12-week-treatment-in-patients/

Efficacy and Safety of AR882, a Selective Uric Acid ... There were no serious adverse events in AR882 treated patients. The most frequently reported adverse event was gout flare occurring in 30% of patients overall ...

8. prnewswire.com prnewswire.com/news-releases/arthrosi-presents-positive-long-term-safety-and-efficacy-data-for-pozdeutinurad-ar882-at-the-european-alliance-of-associations-for-rheumatology-eular-congress-2025-302479045.html

Arthrosi Presents Positive Long-Term Safety and Efficacy ... The Phase 2 study of pozdeutinurad (AR882) in patients with tophaceous gout was a six-month 1:1:1 randomized, global, placebo-controlled study ...