Multi-Dose Safety/Pharmacodynamic Study of SEL-212/SEL-037 in Subjects With Symptomatic Gout & Elevated Blood Uric Acid
Condition: Gout Chronic; Hyperuricemia
MeSH terms: Gout; Hyperuricemia
Intervention: SEL-212; SEL-037; SVP-rapamycin (SEL-110)
Intervention description: SEL-212, biologic; SEL-037, biologic; SVP-rapamycin, biologic
Intervention MeSH terms: Sirolimus; Temsirolimus; MTOR Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 152.0
Sex: All
Minimum age: 21 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This is an open label multicenter study to evaluate the safety and tolerability of multiple
      doses (3 monthly IV infusions) of SEL-212 ( a combination of pegsiticase (SEL-037) and
      SVP-rapamycin (SEL-110)) followed by multiple doses (2 monthly IV infusions) of pegsiticase
      (SEL-037) alone for a total of 5 treatment cycles in subjects with symptomatic gout and
      hyperuricemia. Additional participants will be treated with multiple doses ( 5 monthly IV
      infusions) of pegsiticase (SEL-037) alone.

      Participants will be monitored for safety endpoints through the 5th treatment cycle plus 30
      days .Pharmacokinetic samples will be drawn at pre-determined time points in addition to
      weekly serum uric acid levels.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adult (age 21-75 inclusive) men and women of non child bearing potential with
             established or symptomatic gout which is defined as having at least ONE of any of the
             3 following factors:

               1. ≥ 1 tophus

               2. 1 gout flare within the last 6 months

               3. Chronic gouty arthropathy

          2. Screening serum uric acid of >6 mg/dL

          3. On a gout flare prophylactic regimen for 7 days prior to first dose

          4. Willing to provide written informed consent prior to first study procedure is
             performed.

          5. Understands and is willing and able to comply with study requirements, including the
             schedule of follow-up visits.

        Exclusion Criteria:

          1. History of anaphylaxis or severe allergic reaction.

          2. History of an allergy to pegylated products.

          3. Women of child bearing potential, Defined as:

               -  <6 weeks after surgical bilateral salpingooperhectony with or without
                  hysterectomy

               -  Pre or perimenopausal ( < less than 24 months of natural amenorrhea)

          4. Initiation or change in dose of hormone-replacement therapy for menopausal women less
             than 1 month prior to the Screening Visit or during the Screening Phase would be
             exclusionary. If after being on a stable dose of hormone-replacement therapy for one
             month the patient may be considered for the study if she continues to meet all other
             inclusion and exclusion criteria

          5. Uncontrolled diabetes with baseline HbA1c ≥8%;

          6. Glucose-6-phosphate dehydrogenase deficiency;

          7. Uncontrolled hypertension

          8. Ongoing treatment for arrhythmia, including placement of an implantable defibrillator;

          9. History of coronary artery disease, including myocardial infarction;

         10. Congestive heart failure, New York Heart Association Class III or IV;

         11. ECG with evidence of prior myocardial infarction, clinically significant arrhythmia,
             or other abnormalities that, in the opinion of the investigator, are consistent with
             significant underlying cardiac disease;

         12. History of hematological or autoimmune disorders, is immunosuppressed or
             immunocompromised;

         13. Prior exposure to any experimental or marketed uricase (e.g., rasburicase (Elitek,
             Fasturtec), pegloticase (Krystexxa®), pegsiticase (SEL-037)

         14. History of malignancy within the last 5 years other than basal skin cancer;

         15. Subjects who, in the opinion of the investigator, present with a condition that would
             compromise their safety or that would make study completion unlikely.