Gout
Conditions
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
Sponsors
Selecta Biosciences, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Countries
United States
Outcome results
None listed