Clinical trial: A Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy (NCT04513366)

Eligibility criteria:
Inclusion Criteria:

          1. Has negative results of an FDA Emergency Use Authorized COVID-19 molecular assay for
             detection of SARS-CoV-2 RNA from a respiratory specimen;

          2. History of symptomatic gout defined as:

               1. ≥ 3 gout flares within 18 months of Screening or

               2. Presence of ≥ 1 gout tophus or

               3. Current diagnosis of gouty arthritis

          3. At the Screening Visit: male age 21 - 80 years, inclusive, or female of
             non-childbearing potential age 21-80 years, inclusive, where nonchildbearing potential
             is defined as:

             a. > 6 weeks after hysterectomy with or without surgical bilateral salpingooperhectony
             or b. Post-menopausal (> 24 months of natural amenorrhea or in the absence of >24
             months of amenorrhea, one documented confirmatory FSH measurement)

          4. Has chronic refractory gout defined as having failed to normalize sUA and whose signs
             and symptoms are inadequately controlled with any of the xanthine oxidase inhibitors,
             or for whom these drugs are contraindicated for the patient;

          5. Has at the Screening Visit SUA ≥ 7 mg/dL

          6. Negative serology for HIV-1/-2 and negative antigen to hepatitis B and negative
             antibodies to hepatitis C;

        Exclusion Criteria:

          1. Has a history of anaphylaxis, severe allergic reactions, or severe atopy;

          2. Has a history of any allergy to pegylated products, including, but not limited to
             pegloticase (Krystexxa®), peginterferon alfa-2a (Pegasys®), peginterferon alfa-2b
             (PegIntron®), pegfilgrastim (Neulasta®), pegaptanib (Macugen®), pegaspargase
             (Oncaspar®), pegademase (Adagen®), peg-epoetin beta (Mircera®), pegvisomant
             (Somavert®) certolizumab pegol (Cimzia®), naloxegol (Movantik®), peginesatide
             (Omontys®), and doxorubicin liposome (Doxil®);

          3. Is taking and cannot discontinue known major CYP3A4/P-gp inhibitors or major
             CYP3A4/P-gp inducers at least 14 days before dosing. Patients must remain off these
             medications for the duration of the study, including natural products such as St.
             John's Wort or grapefruit juice.

          4. Is taking drugs known to interact with rapamycin (sirolimus - Rapamune®) such as
             cyclosporine, diltiazem, erythromycin, ketoconazole, posaconazole, voriconazole,
             itraconazole, rifampin, verapamil unless they are stopped 14 days prior to dosing and
             will not be used/prescribed during the trial.

          5. Is a post-menopausal woman that has initiated or had a change in dose of hormone
             replacement therapy (HRT) less than 1 month prior to the Screening Visit or during the
             Screening Phase.

          6. Had a gout flare during Screening that was resolved for less than 1 week prior to
             first treatment with study drug (exclusive of chronic synovitis/arthritis) unless the
             patient has a history of inter-flare intervals of < 1 week.

          7. Has uncontrolled diabetes at Screening with HbA1c ≥ 8.5%;

          8. Has fasting Screening glucose > 240 mg/dL;

          9. Has fasting Screening triglyceride > 500 mg/dL;

         10. Has fasting Screening low-density lipoprotein (LDL) > 200 mg/dL;

         11. Has glucose-6-phosphate dehydrogenase (G6PD) deficiency;

         12. Has uncontrolled hypertension defined as blood pressure > 170/100 mmHg at Screening
             and 1 week prior to dosing

         13. Individual laboratory values which are exclusionary

               -  White blood cell count (WBC) < 3.0 x109/L

               -  Serum aspartate aminotransferase (AST) or alanine amino transferase (ALT) > 3x
                  upper limit of normal (ULN) in the absence of known active liver disease

               -  Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2

               -  Urine albumin creatinine ratio (UACR) > 3.0

               -  Hemoglobin (Hgb) < 9 g/dL

               -  Serum phosphate < 2.0 mg/dL

         14. Is receiving ongoing treatment for arrhythmia, including placement of an implantable
             defibrillator, unless considered stable and on active treatment;

         15. Has evidence of unstable cardiovascular disease or unstable cerebrovascular vascular
             disease. This includes patients who have had a cardiac/vascular event(s) in the last 3
             months including heart attack, stroke or vascular bypass surgery or patients who are
             deemed, by their physician or PI, to have active cardiovascular, cerebrovascular or
             peripheral vascular symptoms/disease inadequately controlled by medication;

         16. Has congestive heart failure, New York Heart Association Class III or IV;

         17. Unless clinically stable and/or appropriately treated, electrocardiogram (ECG) with
             evidence of clinically significant arrhythmia or other abnormalities that, in the
             opinion of the investigator, are consistent with significant underlying cardiac
             disease;

         18. History of significant hematological disorders within 5 years or autoimmune disorders,
             and/or patient is currently immunosuppressed or immunocompromised;

         19. Prior exposure to any experimental or marketed uricase (e.g., rasburicase (Elitek,
             Fasturtec), pegloticase (Krystexxa®®), pegadricase (SEL 037))

         20. Patient has received a live vaccine in the previous 6 months.

         21. Patient is planning to receive any live vaccine during the study.

         22. History of malignancy within the last 5 years other than basal skin cancer;

         23. Patients with a documented history of moderate or severe alcohol or substance use
             disorder within the 12 months prior to randomization.

         24. History of or evidence of clinically severe interstitial lung disease

         25. Immunocompromised state, regardless of etiology
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 19 Years old.
Subject must be at most 80 Years

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