Clinical trial NCT02648269: Safety and Pharmacodynamics of SEL-212 (Pegsiticase + SEL-110) in Subjects With Elevated Blood Uric Acid Levels
Official title: A Phase I Single Ascending Dose Safety, Pharmacokinetic and Pharmacodynamics Study of SEL-212 in Subjects With Elevated Blood Uric Acid
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gout
Lead sponsor: Selecta Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2016-01-07
Enrollment: 63
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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;

Primary outcomes:
measure: Safety and tolerability as assessed by frequency of drug related adverse events, graded by severity
timeFrame: 30 days
Secondary outcomes:
measure: Pharmacokinetics of SEL-110 (AUC)
timeFrame: 30 days
measure: Pharmacokinetics of SEL-037 (AUC)
timeFrame: 30 days
measure: Pharmacodynamics of SEL-037 (blood uric acid levels)
timeFrame: 30 days
measure: Immunogenicity of SEL-037 (measurement of anti-drug antibody levels)
timeFrame: 30 days
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Baptist Health Center for Clinical Research
state: Arkansas
city: Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center, Inc.
state: Florida
city: Baltimore
country: United States
facility: SNBL Clinical Pharmacology Center Inc.
state: Maryland
city: Minneapolis
country: United States
facility: Davita Clinical Research
state: Minnesota
city: Duncansville
country: United States
facility: Altoona Center for Clincal Research
state: Pennsylvania
Study officials:
References:
citation: Sands E, Kivitz A, DeHaan W, Leung SS, Johnston L, Kishimoto TK. Tolerogenic nanoparticles mitigate the formation of anti-drug antibodies against pegylated uricase in patients with hyperuricemia. Nat Commun. 2022 Jan 12;13(1):272. doi: 10.1038/s41467-021-27945-7.