Study of KRYSTEXXA® (Pegloticase) Plus Methotrexate in Participants With Uncontrolled Gout

Inclusion Criteria

• Willing and able to give informed consent.
• Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the study.
• Adult men or women ≥18 years of age.
• Uncontrolled gout, defined as meeting the following criteria:
• Hyperuricemia during the screening period defined as sUA ≥7 mg/dL, and;
• Failure to maintain normalization of sUA with xanthine oxidase inhibitors at the maximum medically appropriate dose, or with a contraindication to xanthine oxidase inhibitor therapy based on medical record review or subject interview, and;
• 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
• Willing to discontinue any oral urate lowering therapy for at least 7 days prior to MTX dosing at Week -6 and remain off when receiving pegloticase infusions.
• Women of childbearing potential (including those with an onset of menopause 160 kg (352 pounds) at Screening.
• Any serious acute bacterial infection, unless treated and completely resolved with antibiotics at least 2 weeks prior to the Week -6 Visit.
• Severe chronic or recurrent bacterial infections, such as recurrent pneumonia or chronic bronchiectasis.
• 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 (3 months or longer) would also meet exclusion criteria.
• History of any transplant surgery requiring maintenance immunosuppressive therapy.
• Known history of hepatitis B virus surface antigen positivity or hepatitis B DNA positivity.
• Known history of hepatitis C virus ribonucleic acid (RNA) positivity.
• Known history of Human Immunodeficiency Virus (HIV) positivity.
• Glucose-6-phosphate dehydrogenase deficiency (tested at the Screening Visit).
• Chronic renal impairment defined as estimated glomerular filtration rate (eGFR) 160/100 mmHg) prior to Randomization at Week -4.
• 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.
• Prior treatment with pegloticase, another recombinant uricase (rasburicase), or concomitant therapy with a polyethylene glycol-conjugated drug.
• Known allergy to pegylated products or history of anaphylactic reaction to a recombinant protein or porcine product.
• Contraindication to MTX treatment or MTX treatment considered inappropriate.
• Known intolerance to MTX.
• Receipt of an investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to MTX administration at Week -6 or plans to take an investigational drug during the study.
• Liver transaminase levels (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) > upper limit of normal (ULN) or albumin < the lower limit of normal (LLN) at the Screening Visit).
• Chronic liver disease.
• White blood cell count < 4, 000/µL, hematocrit < 32 percent, or platelet count < 75,000/µL.
• Currently receiving systemic or radiologic treatment for ongoing cancer.
• History of malignancy within 5 years other than non-melanoma skin cancer or in situ carcinoma of cervix.
• Diagnosis of osteomyelitis.
• Known history of hypoxanthine-guanine phosphoribosyl-transferase deficiency, such as Lesch-Nyhan and Kelley-Seegmiller syndrome.
• Unsuitable candidate for the study, based on the opinion of the Investigator (e.g., cognitive impairment), 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 study.
• Alcohol use in excess of 3 alcoholic beverages per week.
• A known intolerance to all protocol standard gout flare prophylaxis regimens (i.e. sub