Safety and Pharmacodynamics of SEL-212 (Pegsiticase + SEL-110) in Subjects With Elevated Blood Uric Acid Levels

This Study will first evaluate the safety and pharmacokinetics of a single intravenous dose of SEL-110, a nanoparticle containing rapamycin, in subjects with elevated blood uric acid levels. This will be followed, in separate subjects, by evaluation of the safety, pharmacokinetics, pharmacodynamics and immunogenicity of a single intravenous dose of SEL-212, SEL-037 (pegsiticase) plus SEL-110, in subjects with elevated blood uric acid levels. Uricase is an enzyme that converts uric acid to the readily soluble allantoin that is then excreted and SEL-110 is designed to prevent unwanted anti-drug-antibodies (ADAs) from forming. Cohorts of subjects in the SEL-110 only arms of the study will be given a single, ascending intravenous dose of SEL-110 and then monitored for safety and rapamycin levels (pharmacokinetics) over 30 days. Cohorts of subjects in the SEL-212 arms of the study will be given a single, ascending intravenous dose of SEL-110 with a fixed dose of SEL-037 and then monitored for safety, rapamycin levels, SEL-037 levels, uric acid levels and anti-drug-antibodies (ADAs) to SEL-037 for 30 days. One additional control group with receive a single intravenous infusion of SEL-037 at a fixed dose and then monitored for safety, SEL-037 levels, uric acid levels and anti-drug-antibodies (ADAs) to SEL-037 for 30 days

Inclusion criteria

• Male or female subjects ages 21 to 70 inclusive. Female subjects must be of non-childbearing potential;
• Has at the screening visit a serum uric acid ≥ 6 mg/dL, with or without a history of gout;
• The use of allopurinol, febuxostat (Uloric®), or probenecid as uric acid-lowering therapy is permissible if dosing has been stable for at least the month prior to the screening visit;
• Has adequate venous access and able to receive IV therapy;
• Evidence of a personally signed and dated informed consent document indicating that subject has been informed of all pertinent aspects of the study;

Exclusion criteria

• Prior exposure to any experimental or marketed uricase (for arms receiving SEL-037 or SEL-212);
• History of any allergy to pegylated products;
• Glucose-6-phosphate dehydrogenase deficiency or known catalase deficiency;
• History of hematological or autoimmune disorders, is immunosuppressed or immunocompromised;
• Presently taking a drug classified as CYP3A4 inducer or inhibitor;
• Has participated in a clinical trial within 30 days of the Screening;