A Double-blind, Randomized Controlled Trial to Investigate the Efficacy, Safety, and Pharmacokinetics of Pegloticase Administration Via Subcutaneous and Intravenous Routes Both With Methotrexate in Participants With Uncontrolled Gout

Inclusion Criteria

* Participant has provided informed consent before initiation of any trial-specific activities/procedures.
* Age ≥ 18 years or ≥ legal age within the country if it is older than 18 years.
* Participants willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.
* Participants with uncontrolled gout, as meeting the protocol defined criteria.

Exclusion Criteria

* Glucose-6-phosphate dehydrogenase deficiency (tested at the screening visit).
* Liver transaminase levels (aspartate aminotransferase \[AST\] or alanine aminotransferase \[ALT\]) \> 1.25 x upper limit of normal (ULN) or albumin \< the lower limit of normal (LLN) at the screening visit.
* Uncontrolled diabetes mellitus and/or hemoglobin A1c (HbA1c) \> 8%.
* Known intolerance to MTX.
* Participant received prior treatment with pegloticase, another recombinant uricase (ie, rasburicase or pegadricase), or concomitant therapy with a polyethylene glycol (PEG)-conjugated drug.
* A known intolerance to all protocol standard gout flare prophylaxis regimens (ie, participant must be able to tolerate at least 1 of the following: colchicine and/or non-steroidal anti-inflammatory drug and/or low-dose prednisone ≤ 10 mg/day or equivalent dose of other corticosteroid).
* Chronic renal impairment defined as estimated glomerular filtration rate (eGFR) based on Modification of Diet in Renal Disease (MDRD) calculations \< 40 mL/min/1.73 m\^2 or currently on dialysis.