Safety and Pharmacodynamics of SEL-212 (Pegsiticase + SEL-110) in Subjects With Elevated Blood Uric Acid Levels
- Registration Number
- NCT02648269
- Lead Sponsor
- Selecta Biosciences, Inc.
- Brief 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.
- Detailed Description
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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 63
- 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;
- 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;
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SEL-110 SEL-110 Single intravenous dose of SEL-110 SEL-110 SEL-212 Single intravenous dose of SEL-110 SEL-212 SEL-212 Single intravenous dose of SEL-110 plus SEL-037 (pegsiticase) SEL-037 SEL-037 Single intravenous dose of SEL-037 (pegsiticase)
- Primary Outcome Measures
Name Time Method Safety and tolerability as assessed by frequency of drug related adverse events, graded by severity 30 days To assess the safety and tolerability of a single infusion of SEL-110, SEL-212 or SEL-037 as assessed by frequency of drug related adverse events, graded by severity
- Secondary Outcome Measures
Name Time Method Immunogenicity of SEL-037 (measurement of anti-drug antibody levels) 30 days Immunogenicity of SEL-037 by measurement of anti-drug antibody levels over 30 days
Pharmacokinetics of SEL-110 (AUC) 30 days Measurement of the pharmacokinetics of SEL-110 over 30 days by area under the blood concentration versus time curve (AUC)
Pharmacokinetics of SEL-037 (AUC) 30 days Measurement of the pharmacokinetics of SEL-037 over 30 days by area under the serum concentration versus time curve (AUC)
Pharmacodynamics of SEL-037 (blood uric acid levels) 30 days Pharmacodynamics of SEL-037 by measurement of blood uric acid levels over 30 days
Trial Locations
- Locations (6)
Orlando Clinical Research Center, Inc.
🇺🇸Orlando, Florida, United States
Miami Research Associates
🇺🇸Miami, Florida, United States
SNBL Clinical Pharmacology Center Inc.
🇺🇸Baltimore, Maryland, United States
Davita Clinical Research
🇺🇸Minneapolis, Minnesota, United States
Altoona Center for Clincal Research
🇺🇸Duncansville, Pennsylvania, United States
Baptist Health Center for Clinical Research
🇺🇸Little Rock, Arkansas, United States