Pegloticase and Methotrexate Co-administered in Participants With Uncontrolled Gout Who Previously Failed Pegloticase Monotherapy

Exclusion Criteria

• •1. Known history of medically confirmed prior anaphylactic reaction.
• •2. Known history of moderate or severe IR (including but not limited to difficulty in breathing, hypotension, generalized urticaria, generalized erythema, angioedema and/or required treatment with IV steroids or epinephrine; or other serious adverse events (SAEs) related to pegloticase or any other pegylated product treatment.
• •3. Weight \>160 kg (352 pounds) at Screening.
• •4. Any serious acute bacterial infection, unless treated and completely resolved with antibiotics at least 2 weeks prior to the Week 6 Visit.
• •5. Severe chronic or recurrent bacterial infections, such as recurrent pneumonia or chronic bronchiectasis.
• •6. Current or chronic treatment with systemic immunosuppressive agents, such as MTX, azathioprine, cyclosporine, leflunomide, cyclophosphamide or mycophenolate mofetil.
• •7. Current treatment with prednisone \>10 mg/day or equivalent dose of another corticosteroid on a chronic basis (defined as 3 months or longer).
• •8. Known history of any solid organ transplant surgery requiring maintenance immunosuppressive therapy.
• •9. Known history of hepatitis B virus surface antigen positivity or hepatitis B DNA positivity, unless treated, viral load is negative and no chronic or active infection confirmed by hepatitis B virus serology.
• •10. Known history of hepatitis C virus RNA positivity, unless treated and viral load is negative.
• •11. Known history of human immunodeficiency virus positivity.
• •12. glucose-6-phosphate dehydrogenase (G6PD) deficiency (tested at the Screening Visit).
• •13. Severe chronic renal impairment (eGFR \<30 mL/min/1.73 m\^2) at the Screening Visit based on 4 variable Modification of Diet in Renal Disease \[MDRD\] formula or currently on dialysis.
• •14. Non-compensated congestive heart failure, hospitalization for congestive heart failure or treatment for acute coronary syndrome (myocardial infarction or unstable angina) within 3 months of the Screening Visit, current uncontrolled arrhythmia or current uncontrolled blood pressure (\>160/100 mm Hg) prior to Week -6.
• •15. 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.
• •16. Prior treatment with another recombinant uricase (rasburicase) or concomitant therapy with a PEG-conjugated drug.
• •17. Known allergy to pegylated products or history of anaphylactic reaction to a recombinant protein or porcine product.
• •18. Contraindication to MTX treatment or MTX treatment considered inappropriate.
• •19. Known intolerance to MTX.
• •20. Receipt of an investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to MTX administration at Week -6 or plan to take an investigational drug during the trial.
• •21. Current liver disease, as determined by alanine transaminase (ALT) or aspartate transaminase (AST) \>1.25 × upper limit of normal (ULN) or albumin \<lower limit of normal at the Screening Visit.
• •22. Currently receiving systemic or radiologic treatment for ongoing cancer, excluding nonmelanoma skin cancer.
• •23. History of malignancy within 5 years other than non-melanoma skin cancer or in situ carcinoma of cervix.
• •24. White blood cell count \<4.0 × 10\^9/L, hematocrit \<32% or platelet count \<75 × 10\^9/L.
• •25. Diagnosis of osteomyelitis.
• •26. Known history of hypoxanthine-guanine phosphoribosyl-transferase deficiency, such as Lesch-Nyhan and Kelley-Seegmiller syndrome.
• •27. Unsuitable candidate for the trial (e.g., cognitive impairment), based on the opinion of the Investigator, such that participation might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements or complete the trial.
• •28. Alcohol use in excess of 3 alcoholic beverages per week.
• •29. A known intolerance to all protocol standard gout flare prophylaxis regimen (i.e., unable to tolerate any of the following 3 agents: colchicine,nonsteroidal anti-inflammatory drugs (NSAIDs) or low- dose prednisone (≤10 mg/day).
• •30. Current pulmonary fibrosis, bronchiectasis or interstitial pneumonitis. If deemed necessary by the Investigator, a chest x-ray may be performed during Screening.