Clinical trial: Infusion Duration Study To Assess Tolerability of Pegloticase Administered With a Shorter Infusion Duration in Subjects With Uncontrolled Gout Receiving Methotrexate (NCT04511702)

Eligibility criteria:
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.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 39-year-old man comes to the emergency department with an acute onset of severe left toe pain.  The toe is red and exhibits swelling. The patient is not febrile, and does not remember any recent trauma. Medical history is not significant except for the similar attacks and the diagnosis of gouty arthritis. His medication history includes Allopurinol to prevent gouty attacks. His father has the same medical condition. However, his older brother who is 41 years old is healthy with no history of gouty arthritis. Physical examination shows a swollen, tender first metatarsophalangeal joint.  Aspiration of the joint showed high leukocyte count, negative Gram stain, and numerous needle-shaped crystals, which is compatible with gouty arthritis.

Patient description (patient's own words): I'm a 39-year-old man and got admitted to the ER after an unbearable pain in my left toe. My toe was red and terribly swollen. I was still standing on my feet, not febrile and I don't remember hitting my head or anything. I don't have any special medical history, but I had been diagnosed with gout before. I take Lopurin to prevent my gouty attacks. My dad had the same problem, but my 41-year-old brother is healthy and does not have gouty attacks. The doctor did a physical exam and found that the joints between my toes and the rest of my foot were swollen and tender. The doctor renewed his diagnosis of gouty arthritis.

Does the patient match the trial criteria? Contradiction