A Study to Investigate the Clinical Effect and the Safety of PRX-115 Infused Intravenously at Different Dosing Regimens, With and Without Methotrexate, Versus Placebo in Adults Gout Patients (RELEASE)

Inclusion criteria

• Males or females ≥18 years of age.
• Weight within the range of 50.0 - 150.0 kg.
• Gout patients who failed to normalize sUA (\<7 mg/dL) with or without xanthine oxidase inhibitors or uricosuric agent or have contraindications to these drugs.
• Willing to discontinue any oral ULT
• Females who are sterile, postmenopausal, or non-pregnant and using birth control methods.

Exclusion criteria

• Any condition known to have arthritis as a clinical manifestation.
• Positive testing for HBV,HCV, or HIV.
• The patient is a pregnant or lactating female or plans to become pregnant during the study period.
• Known allergy or sensitivity to the injected proteins, including pegylated products.
• Prior exposure to any experimental or marketed uricase.
• Patient treated with a medication known to have an influence on urate metabolism or clearance such as ULTs.
• History of anaphylaxis, severe allergic reactions, or severe atopy.
• G6PD deficiency or known catalase deficiency.
• History of significant hematologic or autoimmune disorders within 5 years of Screening and/or patient is immunocompromised or treated with immunosuppressive medications.
• Non-compensated CHF or hospitalization for CHF (Stage 3-4 NYHA Functional Class) within 3 months of the Screening Visit, uncontrolled arrhythmia, treatment for acute coronary syndrome (myocardial infarction or unstable angina), or uncontrolled BP (\>160/100 mmHg) at screening and prior to randomization at Week -4 (Visit 1).
• Current liver disease, as determined by ALT or AST levels above upper limit of normal at Screening Visit.
• Chronic liver disease.
• Hemoglobin \<11 g/dL, neutrophil count \<1500 /µl, or platelet count \<100,000 /µl.
• Known severe pulmonary fibrosis, bronchiectasis or interstitial pneumonitis.
• eGFR ≤ 40 mL/min/1.73m2 tested at Screening Visit. Kidney transplant or requires dialysis.
• Known intolerance and/or known contraindication to MTX treatment or MTX treatment considered inappropriate
• Has uncontrolled type 2 diabetes at Screening with HbA1c ≥8.5%. Patients with type 1 diabetes will be excluded.
• Has known latent autoimmune diabetes of adult.
• Immunocompromised state, regardless of etiology.
• History or treatment of malignancy in the last 5 years, excluding localized, nonmelanoma skin cancers (e.g. basal or squamous cell)