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

Study Overview
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Brief Summary
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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
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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

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

Conditions
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Gout

Intervention / Treatment
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* Drug: SEL-110
* Biological: SEL-212
* Biological: SEL-037


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SEL-110<br>Single intravenous dose of SEL-110 | Drug: SEL-110<br> <br> Biological: SEL-212<br> <br> |
| Experimental: SEL-212<br>Single intravenous dose of SEL-110 plus SEL-037 (pegsiticase) | Biological: SEL-212<br> <br> |
| Experimental: SEL-037<br>Single intravenous dose of SEL-037 (pegsiticase) | Biological: SEL-037<br> <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-110, SEL-212 or 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-110 (AUC) | Measurement of the pharmacokinetics of SEL-110 over 30 days by area under the blood concentration versus time curve (AUC) | 30 days | 
| 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 |