Safety and Efficacy Study of Intramuscular Uricase-PEG 20

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, pharmacokinetics and pharmacodynamics of single and multiple intramuscular doses of Uricase-PEG 20

Detailed Description
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Uricase is an enzyme (found in most mammals but not humans) that converts poorly soluble uric acid into highly soluble allantoin. Because humans lack uricase, they are prone to develop elevated levels of uric acid, which can form crystals in the joints and soft tissues. In those which chronically elevated uric acid, gout may develop. In the setting of acute rises in uric acid, seen for example in tumor lysis syndrome, uric acid crystals can damage the renal tubules. Uricase-PEG 20 is a recombinant uricase conjugated with multiple PEG molecules designed to prolong the half-life and decrease the immunogenicity of uricase. This study will characterize the safety, pharmacokinetics and pharmacodynamics of intramuscular Uricase-PEG 20, the anticipated route of administration to be used in future clinical development in gout.

Official Title
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A Cohort Dose-Escalation Phase 1 Study of Intramuscular Injection of Uricase-PEG 20

Conditions
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Gout, Hyperuricemia

Intervention / Treatment
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* Biological: Uricase-PEG 20


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Serum uric acid > 6 mg/dL (men) or > 5 mg/dL (women) Clinical laboratory values within normal limits or not clinically significant Women should be menopausal or peri-menopausal Exclusion Criteria: Prior exposure to uricase History of severe allergic reactions, or any allergy to PEG or pegylated products G6PD or catalase deficiency Medical condition that may interfere with ability to complete the study (e.g., uncontrolled diabetes or hypertension, congestive heart failure NYHA Class III or IV, history of myocardial infarction, immunosuppression, pregnancy)

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Uricase-PEG 20<br>Cohorts will receive ascending doses of Uricase-PEG 20 in a sequential manner. The study will enroll both single dose cohorts and multi-dose cohorts. | Biological: Uricase-PEG 20<br>* Intramuscular injection of Uricase-PEG 20 without premedication<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (assessment of signs and symptoms and clinical laboratory measurements following administration of Uricase-PEG 20, graded according to the Common Toxicity Criteria for Rheumatology, version 2.0) |  | Up to 35 days after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (Uricase-PEG 20 serum concentration) |  | Up to 35 days after dosing | 
| Pharmacodynamics (plasma uric acid concentration) |  | Up to 35 days after dosing | 
| Immunogenicity |  | Up to 35 days after dosing |