A Phase Ib Clinical Trial of Peguricase for Injection With Methotrexate in Patients With Uncontrolled Gout.

Inclusion Criteria:

• Willing and able to give informed consent.
• Male and female aged between 18 and 70 years old , regardless of gender.
• Male weight ≥50 kg, female weight ≥45 kg, body mass index (BMI) in the range of (19-30) kg/m2 (including 19 and 30)；
• The clinical diagnosis of gout met the criteria of American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) in 2015，patients were in non-acuteattack at screening or at least 2 weeks after complete remission of acute attack, andsUA ≥420 μmol/L at screening；
• Patients whose serum uric acid level could not reach the target after standardtreatment with conventional uric acid-lowering drugs or who were contraindicated orintolerant to conventional uric acid-lowering drugs；
• Patients who were willing to stop taking any uric-acid-lowering drug at least 7 daysbefore using methotrexate during the run-in period;
• Could tolerate the prescribed dose of methotrexate during the run-in period;
• Patients were able to attend and complete the visit on time.

Exclusion Criteria:

• Patients had active systemic infection within 2 weeks before enrollment，including aninfection for which treatment was being received；
• Having a chronic or recurrent infection, such as recurrent pneumonia or chronicbronchitis; Patients with active or severe lung disease or pulmonary insufficiency onchest imaging, or current pulmonary fibrosis or bronchiectasis；
• Patients who are on anti-TB treatment or have active TB；
• Diagnosis of osteomyelitis；
• Ongoing or long-term use of immune system modulating drugs, such as methotrexate,mercaptopurine, mycophanolate, long-term use (≥3 months) of prednisone ≥10 mg/ day orequivalent dose of corticosteroids; Or have a history of transplant surgery requiringlong-term immunotherapy; Or a known history of autoimmune disease, allergic disease;
• Known allergy to recombinant proteins or porcine products, or history of allergy touricase, pegylated products, corticosteroids and antihistamines, or known intoleranceto methotrexate, fexofenadine, acetaminophen or contraindications to methotrexate,fexofenadine, acetaminophen;
• Patients who are known to be intolerant to all gout attack management regiments (participants must be able to tolerate at least one: Colchicine and/or Nsaids and/orPrednisone 0.5 mg/kg daily；
• Patients who have previously been treated with pegyluricase or other recombinanturicase, or who have been treated with other pegylated biological products;
• Participation in other clinical study with a drug intervention within 4 weeks beforeinitiation of methotrexate or the drug was still in the elimination phase beforescreening (within 5 half-lives), whichever is older;
• Patients with chronic liver disease such as hepatitis, cirrhosis, alcoholic liverdisease;
• Patients have unstable angina, severe arrhythmias requiring drug intervention,congestive heart failure (NYHA grade≥Ⅱ), uncontrolled hypertension (over 150/95 mmHg),poor glycemic control in diabetics ( HbA1c≥7%), acute stroke, Severe or chronichemorrhagic digestive disease, pleural and abdominal effusion;
• A history of hypoxanthine-guanine phosphoribosyltransferase deficiency, such asLesch-Nyhan and Kelley-Seegmiller syndrome;
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency or G6PD test values below thelower limit of normal;
• Estimated glomerular filtration rate (eGFR) ≤40 mL/min/1.73m2, or currently receivingdialysis, or end-stage renal disease (CKD4-5);
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above the upperlimit of normal value or albumin below the lower limit of normal value duringscreening (before methotrexate treatment);
• Use of any blood component, short-acting or long-acting growth factor drugs within 14days prior to screening, or white blood cell count < 4×109/L, hematopoietic volume < 32%, or platelet count < 75×109/L;
• Receiving anticoagulant therapy or international normalized ratio (INR) > 1.5×ULN oractivated partial thromboplastin time (APTT) > 1.5×ULN before enrollment;
• Receiving systemic or local radiotherapy for tumors, or history of malignancy within 5years other than non-melanoma skin cancer or in situ carcinoma of cervix;
• Any acute illness that was considered by the investigator to be likely to affect thestudy occurred within 1 month before screening;
• Donated (or lost) blood and donated (or lost) ≥400 mL or received blood transfusionwithin 3 months before screening;
• If any one of the five serological tests of hepatitis B was positive except forhepatitis B surface antibody, or hepatitis C antibody positive, treponema pallidumantibody positive or HIV antibody positive in serum virology examination;
• History of drug or substance abuse, or a positive drug screening test;
• History of alcohol abuse in the 3 months before screening [drinking more than 14 unitsof alcohol per week (1 unit ≈360 mL of beer)] or 45 mL of 40% spirits or 150 mL ofwine)]; or positive alcohol breath test on admission;
• Lactating women, as well as male participants (or their partners) or femaleparticipants 30 days before the study to the end of the study, who have plans forpregnancy or sperm or egg donation within 6 months and are unwilling to take effectivecontraceptive measures;
• Patients have serious mental and psychological disorders, cognitive disorders and theexistence of a history of mental illness.
• The investigator considered it inappropriate to participate in the study.