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

Gout Clinical Trial

Official title:

A Phase I Single Ascending Dose Safety, Pharmacokinetic and Pharmacodynamics Study of SEL-212 in Subjects With Elevated Blood Uric Acid

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02648269
• Other study ID #: SEL-212/101
• Status: Completed
• Phase: Phase 1
• First received: January 5, 2016
• Last updated: January 26, 2017
• Start date: December 2015
• Est. completion date: December 2016

Study information

• Verified date: January 2017
• Source: Selecta Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 70 Years

Eligibility

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;

Related Conditions & MeSH terms

• Gout

Intervention

Drug:
• SEL-110

Biological:
• SEL-212

• SEL-037

Locations

Country	Name	City	State
United States	SNBL Clinical Pharmacology Center Inc.	Baltimore	Maryland
United States	Altoona Center for Clincal Research	Duncansville	Pennsylvania
United States	Baptist Health Center for Clinical Research	Little Rock	Arkansas
United States	Miami Research Associates	Miami	Florida
United States	Davita Clinical Research	Minneapolis	Minnesota
United States	Orlando Clinical Research Center, Inc.	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Selecta Biosciences, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability as assessed by frequency of drug related adverse events, graded by severity	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	30 days
Secondary	Pharmacokinetics of SEL-110 (AUC)	Measurement of the pharmacokinetics of SEL-110 over 30 days by area under the blood concentration versus time curve (AUC)	30 days
Secondary	Pharmacokinetics of SEL-037 (AUC)	Measurement of the pharmacokinetics of SEL-037 over 30 days by area under the serum concentration versus time curve (AUC)	30 days
Secondary	Pharmacodynamics of SEL-037 (blood uric acid levels)	Pharmacodynamics of SEL-037 by measurement of blood uric acid levels over 30 days	30 days
Secondary	Immunogenicity of SEL-037 (measurement of anti-drug antibody levels)	Immunogenicity of SEL-037 by measurement of anti-drug antibody levels over 30 days	30 days