A Trial to Investigate the Non-inferiority of Pegloticase Administered Every 4 Weeks (Q4W) With MTX Compared With Every 2 Weeks (Q2W) With MTX in Participants With Uncontrolled Refractory Gout

Acquired from Horizon in 2024.

Inclusion criteria

• 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 participant interview, and;
• Symptoms of gout
• Willing to discontinue any oral ULT for at least 7 days prior to MTX dosing at Week -4 and continue not receiving any oral ULT when receiving pegloticase/placebo for pegloticase infusions
• Women of childbearing potential must have negative serum/urine pregnancy tests during screening and Week -4.
• Men who are not vasectomized must agree to use appropriate contraception, so as to not impregnate a female partner of reproductive potential during the trial.

Exclusion criteria

• 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)
• 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 RNA positivity, unless treated and viral load is negative
• Known history of human immunodeficiency virus (HIV) positivity
• G6PD deficiency (quantitative test at the Screening Visit centrally or locally)
• Non-compensated congestive heart failure or hospitalization for congestive heart failure within 3 months of the Screening Visit, uncontrolled arrhythmia, treatment for acute coronary syndrome (myocardial infarction or unstable angina) or uncontrolled blood pressure (> 160/100 mmHg) prior to 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 PEG-conjugated drug
• Unable to tolerate MTX 15 mg orally during the MTX Run-in Period
• Chronic liver disease
• White blood cell count < 4,000/μL, hematocrit < 32% 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
• A known intolerance to all protocol-standard gout flare prophylaxis regimens (i.e., participant must be able to tolerate at least 1 of the following: colchicine and/or non-steroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day)
• Current pulmonary fibrosis, bronchiectasis or interstitial pneumonitis. If deemed necessary by the Investigator, a chest X-ray may be performed during Screening.