safety and pharmacodynamics of sel-212 (pegsiticase + sel-110) in subjects with elevated blood uric acid levels

Conditions: Gout

Summary: 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.

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

Eligibility criteria:
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;