Infusion Duration Study To Assess Tolerability of Pegloticase Administered With a Shorter Infusion Duration in Subjects With Uncontrolled Gout Receiving Methotrexate

Inclusion Criteria:

1. Adult men or women ≥18 years of age.

2. Uncontrolled gout, defined as meeting the following criteria:

   • Hyperuricemia during the screening period defined as sUA ≥6 mg/dL
   • Failure to maintain normalization of sUA with xanthine oxidase inhibitors at the maximum medically appropriate dose, or with intolerable side effects or a contraindication to xanthine oxidase inhibitor therapy based on medical record review or subject interview

   • Symptoms of gout including at least 1 of the following:

     • Presence of at least one tophus
     • Recurrent flares defined as 2 or more flares in the past 12 months prior to screening
     • Presence of chronic gouty arthritis
3. Willing to discontinue all oral urate-lowering therapy at least 7 days prior to MTX dosing at Week -4 and remain off of urate lowering therapy when receiving pegloticase infusions during the study.
4. Able to tolerate MTX 15 mg for 4 weeks during the MTX Run-in Period prior to the first dose of pegloticase.

Exclusion Criteria:

1. Current or chronic treatment with systemic immunosuppressive agents such as MTX,azathioprine, or mycophenolate mofetil; prednisone ≥10 mg/day or equivalent dose of other corticosteroid on a chronic basis (defined as 3 months or longer) would also meet exclusion criteria.
2. Known history of any solid organ transplant surgery requiring maintenance Immunosuppressive therapy unless treated and no chronic or active infection confirmed by HBV serology.
3. Known history of hepatitis B virus surface antigen positivity or hepatitis B DNA positivity, unless treated and viral load is negative and no chronic or active infection confirmed by HBV serology.
4. Known history of Human Immunodeficiency Virus (HIV) positivity.
5. Glucose-6-phosphate dehydrogenase (G6PD) deficiency (tested at Screening Visit).
6. Severe chronic renal impairment (estimated glomerular filtration rate <40 mL/min/1.73 m2) at the Screening Visit based on 4 variable-Modification of Diet in Renal Disease [MDRD] formula or currently on dialysis.
7. Non-compensated congestive heart failure or hospitalization for congestive heart failure or treatment for acute coronary syndrome (myocardial infarction or unstable angina) within 3 months of the Screening Visit, or current uncontrolled arrhythmia, or current uncontrolled blood pressure (BP) (>160/100 mmHg) prior to Week -4.
8. Pregnant, planning to become pregnant, breastfeeding, planning to impregnate female partner, or not on an effective form of birth control, as determined by the Investigator.
9. Prior treatment with pegloticase (KRYSTEXXA), another recombinant uricase (rasburicase), or concomitant therapy with a polyethylene glycol-conjugated drug.
10. Known intolerance to MTX.
11. Chronic liver disease.
12. Currently receiving systemic or radiologic treatment for ongoing cancer.
13. History of malignancy within 5 years other than non-melanoma skin cancer or in situ carcinoma of cervix.
14. Known history of hypoxanthine-guanine phosphoribosyl-transferase deficiency, such as Lesch-Nyhan and Kelley-Seegmiller syndrome.
15. Current pulmonary fibrosis, bronchiectasis or interstitial pneumonitis. If deemed necessary by the Investigator, a chest X-ray may be performed during Screening.