Clinical trial NCT01038947: Safety and Efficacy Study of Intramuscular Uricase-PEG 20
Official title: A Cohort Dose-Escalation Phase 1 Study of Intramuscular Injection of Uricase-PEG 20
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Gout
Hyperuricemia
Lead sponsor: EnzymeRx
Sponsor class: INDUSTRY
First posted: 2009-12-24
Enrollment: 28
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: 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)
timeFrame: Up to 35 days after dosing
Secondary outcomes:
measure: Pharmacokinetics (Uricase-PEG 20 serum concentration)
timeFrame: Up to 35 days after dosing
measure: Pharmacodynamics (plasma uric acid concentration)
timeFrame: Up to 35 days after dosing
measure: Immunogenicity
timeFrame: Up to 35 days after dosing
Other outcomes:
Locations:
city: Miami
country: United States
facility: MRA Clinical Research
state: Florida
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
Study officials:
affiliation: EnzymeRx, LLC
name: Anthony S Fiorino, MD, PhD
role: STUDY_DIRECTOR
affiliation: MRA Clinical Research
name: Patricia Pardo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bomalaski JS, Holtsberg FW, Ensor CM, Clark MA. Uricase formulated with polyethylene glycol (uricase-PEG 20): biochemical rationale and preclinical studies. J Rheumatol. 2002 Sep;29(9):1942-9.