Clinical Trials

Gout is an inflammatory arthritic disease resulting from urate crystal accumulation in and around joint tissues. It is frequently associated with comorbidities such as metabolic syndrome, cardiovascular disease, and chronic kidney disease. Urate lowering therapy is effective for managing chronic gout by maintaining serum urate (sUA) levels below 5 to 6 mg/dL. Allopurinol is first line therapy of gout in ACR guidelines. However, on average, 10-30% of patients do not respond and are intolerant to allopurinol. The second line therapy, febuxostat recently received a black box warning from FDA for cardiovascular risk. Due to poor tolerability, pegloticase is a third-line treatment and is reserved for patients with severe gout or those refractory to conventional therapy. Currently there is no gout medication which consistently lowers serum urate levels below 5 mg/dL to achieve clinical benefits such as flare and/or tophi reduction.

AR882 is a potent uricosuric drug undergoing development for the treatment of gout. In a phase 2a study in gout patients (Figure 1), AR882 50 mg alone reduced sUA levels to <5 mg/dL in 93% of patients, versus 11% and 33% for allopurinol 300 mg and febuxostat 40 mg alone, respectively. When AR882 50 mg was administered with allopurinol 300 mg , 100% of subjects had sUA levels <4 mg/dL and over 40% had levels below 3 mg/dL. Similarly, in patients who received AR882 50 mg with febuxostat, almost 80% of subjects achieved sUA levels < 3 mg/dL, which is up to 71% sUA reduction over baseline. In contrast, no patients on allopurinol or febuxostat alone achieved levels below 4 mg/dL. AR882 75 mg showed similar effect to combination of AR882 50 mg with allopurinol or febuxostat.

 

 

Figure 1. Response Rates of AR882 Alone or In Combination with Xanthine Oxidase Inhibitors (Allopurinol or Febuxostat)

 

Clinical Study Description Status Study Outcome
AR882-101 Phase 1 Single Ascending Doses of AR882 in Healthy Male Adults NCT04347005 Completed Published in 2019 Conference of American College of Rheumatology, Atlanta

 

AR882-102 Phase 1 Multiple Ascending Dose Study of AR882 in Healthy Male Adults NCT04314986 Completed Published in 2020 American College of Rheumatology Convergence

 

AR882-103 Phase 1 AME Study of [14C]AR882 in Healthy Male Adults NCT04508426 Completed Published in 2021 American College of Rheumatology Convergence
AR882-104 Phase 1 Pharmacokinetic and Pharmacodynamic Study of AR882 in Subjects with Various Degrees of Renal Impairment NCT04646889 Ongoing Published in 2021 American College of Rheumatology Convergence
AR882-201 Phase 2a Study of AR882 Alone or in Combination with Febuxostat or Allopurinol in Gout Patients NCT04155918 Completed Published in 2020 American College of Rheumatology Convergence and 2021 European League against Rheumatism (EULAR) Convergence

 

AR882-202 Phase 2b Randomized Study to Evaluate the Safety and Efficacy of AR882 versus Placebo in Gout Patients Ongoing Future publication
AR882-203 Phase 2 Randomized Study to Evaluate the Safety and Efficacy of AR882 versus Allopurinol in Patients with Tophaceous Gout Planning Future publication