AR882 for Gout

Recruiting at 73 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Arthrosi Therapeutics

Disqualifiers: Malignancy, Pregnant, Kidney stones, others

Pivotal Trial (Near Approval)

Prior Safety Data

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

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications. However, it mentions that patients on approved urate-lowering therapy (ULT) can participate if their serum uric acid levels are above a certain threshold, suggesting you might be able to continue those medications.

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

The research on Arhalofenate (ARH), which is similar to AR882, shows it has uricosuric (helps remove uric acid from the body) and anti-flare activities when used with febuxostat, suggesting potential effectiveness in lowering serum uric acid levels in gout patients. ^{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. It works by activating AMP-activated protein kinase (AMPK) signaling and blocking URAT1, which is different from many other gout medications that primarily focus on uric acid reduction. ^{4 6 7 8 9}

Research Team

Robert Keenan, MD

Principal Investigator

Arthrosi Therapeutics, Inc.

Eligibility Criteria

This trial is for gout patients who need treatment to lower their uric acid levels. Specific eligibility details are not provided, but typically participants must meet certain health standards and not have conditions that could interfere with the study or pose additional risks.

Inclusion Criteria

My weight is at least 50 kg.

I have had gout before.

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

Exclusion Criteria

Pregnant or breastfeeding

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

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

Trial 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

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• AR882 (Xanthine Oxidase Inhibitor)

Trial Overview The trial is testing the effectiveness of a new medication called AR882 in two different doses (50 mg and 75 mg) against a placebo over a period of one year to see if it can reduce uric acid levels in people with gout.

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]

A systematic review of 20 articles found that various interventions, particularly nurse-led programs, significantly improved patient adherence to urate-lowering therapy (ULT) and reduced serum urate (SU) levels in gout patients.

Nurse-led interventions were especially effective as they empowered patients through education and ongoing support, while pharmacist-led and multidisciplinary approaches also contributed to better medication adherence and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interventions to improve uptake of urate-lowering therapy in patients with gout: a systematic review. Gill, I., Dalbeth, N., 'Ofanoa, M., et al.[2020]

A 12-week treatment combining allopurinol and movalis significantly reduced the frequency of gout flare-ups and improved patients' quality of life, with over two-thirds of patients experiencing no worsening of joint symptoms.

The therapy was well-tolerated, showing no significant adverse effects or changes in blood pressure or kidney function, and 90.9% of patients rated their treatment outcome as very good.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of a 12-week allopurinol-lowering therapy in combination with the non-steroidal anti-inflammatory drug meloxicam in patients with gout]. Gromova, MA., Tsurko, VV., Kislyak, OA., et al.[2022]

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]

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 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]

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

Interventions to improve uptake of urate-lowering therapy in patients with gout: a systematic review. [2020]

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Evaluation of a 12-week allopurinol-lowering therapy in combination with the non-steroidal anti-inflammatory drug meloxicam in patients with gout]. [2022]

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. 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]

7. 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]

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

Innate immunity conferred by Toll-like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal-induced inflammation. [2022]

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

The murine homolog of the interleukin-8 receptor CXCR-2 is essential for the occurrence of neutrophilic inflammation in the air pouch model of acute urate crystal-induced gouty synovitis. [2007]