Phase 2 to Assess Efficacy and Safety in AR882 Alone or in Combination With Allopurinol in Patients With Tophaceous Gout

Study Overview
=================
Brief Summary
-----------------
This study will assess the serum urate lowering effect, tophi reduction, and safety of AR882 alone and in combination with allopurinol in patients with tophaceous gout at two doses compared to allopurinol over 24 weeks.

Official Title
-----------------
A Phase 2, Randomized, Open-Label, Allopurinol-Controlled, Multicenter Study With Optional Extension to Evaluate the Safety and Efficacy of AR882 Alone or in Combination With Allopurinol in Tophaceous Gout Patients

Conditions
-----------------
Gout, Arthritis, Gouty, Hyperuricemia, Gout Chronic

Intervention / Treatment
-----------------
* Drug: AR882 Dose 1
* Drug: AR882 Dose 2
* Drug: Allopurinol Tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: History of gout at least 1 measurable tophus on the hands/wrists and/or feet/ankles ≥ 5 mm and ≤ 30 mm in the longest diameter. Patients who are NOT on approved ULT must have sUA > 7 mg/dL Patients who are on medically appropriate ULT must have sUA > 6 mg/dL Estimated Glomerular Filtration Rate (eGFR) ≥ 45 mL/min/1.73m2 Exclusion Criteria: Malignancy within 5 years, except for successfully treated basal or squamous cell carcinoma of the skin Pregnant or breastfeeding History of kidney stones

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>Allopurinol once daily for 24 weeks | Drug: Allopurinol Tablet<br>* Solid tablet<br>|
| Experimental: Group 2<br>AR882 Dose 1 x 2 weeks, then Dose 2 x 22 weeks | Drug: AR882 Dose 1<br>* Solid Oral Capsule<br>Drug: AR882 Dose 2<br>* Solid Oral Capsule<br>|
| Experimental: Group 3<br>AR882 Dose 1 + Allopurinol for 24 weeks | Drug: AR882 Dose 1<br>* Solid Oral Capsule<br>Drug: Allopurinol Tablet<br>* Solid tablet<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum urate (uric acid) (sUA) level < 5 mg/dL at month 3 | Comparison of the treatment groups for the proportion of patients with serum urate (uric acid) (sUA) level < 5 mg/dL at month 3 | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in tophus area at Months 3 and 6 | Comparison of the treatment groups for tophus area as measured by digital calipers | 12 weeks and 24 weeks | 
| Change from baseline in tophus crystal volume at Months 6 | Comparison of the treatment groups for tophus crystal as measured by Dual-energy computerized tomography. | 24 weeks | 
| Serum urate (uric acid) (sUA) level <6, <4 and <3 mg/dL at month 3 | Comparison of the treatment groups for the proportion of patients with serum urate (uric acid) (sUA) level <6, <4 and <3 mg/dL at month 3 | 12 weeks | 
| Serum urate (uric acid) (sUA) level <6, < 5, <4 and <3 mg/dL at month 6 | Comparison of the treatment groups for the proportion of patients with serum urate (uric acid) (sUA) level <6, < 5, <4 and <3 mg/dL at month 6 | 24 weeks | 
| Incidence of Adverse Events | Treatment Emergent Adverse Events and Serious Adverse Event incidence. | 24 weeks |