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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Gout

Intervention / Treatment
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* Biological: SEL-037 (pegsiticase)


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SEL-037 (pegsiticase)<br>Pegylated uricase | Biological: SEL-037 (pegsiticase)<br>* Intravenous infusion of SEL-037<br>|

What is the study measuring?
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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 |