Safety and Pharmacodynamics of SEL-037 (Pegsiticase) in Subjects With Elevated Blood Uric Acid Levels

An Open-Label, Sequential, Ascending Single-Dose Safety, Tolerability, Pharmacokinetic and Pharmacodynamics Study of an Intravenous Infusion of SEL-037 in Subjects With Elevated Blood Uric Acid Levels

This Study will evaluate the safety, pharmacokinetics, pharmacodynamics and immunogenicity of a single intravenous infusion of SEL-037 (pegsiticase), a pegylated uricase, 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.

Study Overview

• Status: Completed
• Conditions: Gout
• Intervention / Treatment: Biological: SEL-037 (pegsiticase)

Detailed Description

This Study will evaluate the safety, pharmacokinetics, pharmacodynamics and immunogenicity of a single intravenous infusion of SEL-037 (pegsiticase), a pegylated uricase, 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. Cohorts of Subjects will be given a single, ascending dose intravenous infusion of SEL-037 and then monitored for safety, uric acid levels and anti-drug-antibodies (ADAs) to SEL-037 for 30 days.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clincal Research
  • Texas
    • Dallas, Texas, United States, 75231
      • Metroplex Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects ages 21 to 75 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;
• 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;
• Has participated in a clinical trial within 30 days of the Screening;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SEL-037 (pegsiticase); Pegylated uricase	Biological: SEL-037 (pegsiticase); Intravenous infusion of SEL-037

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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-037 as assessed by frequency of drug related adverse events, graded by severity	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Pharmacodynamics of SEL-037 (blood uric acid levels)	Pharmacodynamics of SEL-037 by measurement of blood uric acid levels over 30 days	30 days
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

Collaborators and Investigators

• Sponsor: Selecta Biosciences, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: May 29, 2015
• First Submitted That Met QC Criteria: June 4, 2015
• First Posted (Estimate): June 8, 2015

Study Record Updates

• Last Update Posted (Estimate): October 21, 2016
• Last Update Submitted That Met QC Criteria: October 19, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: SEL-037/101