A Study to Evaluate the Safety, Tolerability, PK, and PD Properties of PRX-115 in Adult Volunteers With Elevated Uric Acid Levels

Study Overview
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Brief Summary
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This is a Phase 1, double-blind, placebo-controlled, single dose-ascending study in participants with elevated uric acid levels. This study will be conducted in approximately 56 adult male and female participants in the dose escalation phase.

Detailed Description
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Participants will be assigned to 1 of 7 sequential dosing cohorts, each composed of 8 (6 active + 2 placebo) participants who will receive a single dose of PRX-115 or placebo by intravenous (IV) infusion.

Official Title
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A Double-blind, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Properties of PRX-115 in Adult Volunteers With Elevated Uric Acid Levels.

Conditions
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Gout

Intervention / Treatment
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* Drug: PRX-115
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females 18 to 65 years of age, inclusive. Serum uric acid greater than 6.0 mg/dL (0.35 mmol/L) at the Screening visit. Body mass index within the range 18.5 to 40 kg/m^2, inclusive, at the Screening visit. Women of childbearing potential may be included only if they have a negative beta human chorionic gonadotropin (β-hCG) test result at Screening. Men and women of childbearing potential and their partners should use double barrier contraception. Exclusion Criteria: Has any condition known to have arthritis as a clinical manifestation Had greater than or equal to 1 gout flare in the last year prior to either Screening or Day -1. Has clinical evidence of subcutaneous tophi at either Screening or Day -1. Estimated glomerular filtration rate (eGFR) value less than or equal to 60 mL/min/1.73m^2 History of significant renal disease, and/or presence of renal stones at either Screening or Day -1. Has a history of anaphylaxis, severe allergic reactions, or severe atopy. History of autoimmune disorders, and/or participant is immunocompromised or treated with immunosuppressive medications. Has evidence of cardiovascular or cerebrovascular disease. History of congestive heart failure, New York Heart Association Class III or IV. BP outside the range of 90 to 150 mm Hg for systolic or 50 to 95 mm Hg for diastolic. Participants with hypertension who are not on stable medication for at least 6 months. Has uncontrolled type 2 diabetes Concurrent treatment with urate lowering drugs (ULDs). Prior exposure to any experimental or marketed uricase (eg, rasburicase [Elitek, Fasturtec], pegloticase [Krystexxa®], pegadricase [SEL-212]). Glucose-6-phosphate dehydrogenase (G6PD) deficiency or known catalase deficiency.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRX-115<br>Participants will receive a single dose of PRX-115 by IV infusion | Drug: PRX-115<br>* Escalating doses of PRX-115 will be given in different cohorts i.e., Cohorts 1 through 7<br>* Other names: Escalating doses of PRX-115;|
| Placebo Comparator: Placebo<br>Participants will receive a single dose of placebo by IV infusion | Drug: Placebo<br>* Escalating doses of Placebo will be given in different cohorts i.e., Cohorts 1 through 7<br>* Other names: Placebo to match;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events receiving PRX-115 compared to placebo | To assess the safety and tolerability of a single infusion of PRX-115 as assessed by frequency of drug related adverse events, graded by severity. | Day 0 - Day 85 | 
| Number of participants with abnormal clinically significant clinical laboratory results | Clinical laboratory tests include hematology, coagulation and biochemistry | Day 0 - Day 85 | 
| Number of participants with abnormal clinical vital signs | Vital signs include pulse rate, blood pressure, respiratory rate and tympanic temperature | Day 0 - Day 85 | 
| Number of participants with abnormal clinically significant results from physical examination |  | Day 0 - Day 85 | 
| Number of participants with abnormal clinically significant 12-lead electrocardiogram (ECG) parameters |  | Day 0 - Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK of PRX-115: Maximum observed plasma drug concentration (Cmax) | The Cmax PK parameter calculated based on the observed plasma drug concentration versus time curve | Day 1 - Day 85 | 
| PK of PRX-115: Area under the plasma concentration versus time curve (AUC 0-t) | The PK parameter calculated will be Area under the plasma drug concentration-time curve of the last measurable drug concentration (AUC0-t). | Day 1 - Day 85 | 
| PK of PRX-115: Time to maximum observed plasma drug concentration (Tmax) | The PK parameter calculated will be Time to maximum observed plasma drug concentration (T max). | Day 1 - Day 85 | 
| PK of PRX-115: total body clearance (CL) | The PK parameter calculated will be total body clearance (CL). | Day 1 - Day 85 | 
| PK of PRX-115: volume of distribution during the terminal phase (Vd) | The PK parameter calculated will be volume of distribution during the terminal phase (Vd). | Day 1 - Day 85 | 
| PK of PRX-115: Terminal elimination half-life (T ½) | The PK parameter of Terminal elimination half-life (T ½) is calculated based on the plasma drug concentration-time curve | Day 1 - Day 85 | 
| PK of PRX-115: Area under the plasma concentration versus time curve (AUC 0-inf) | The PK parameters calculated will be Area under the plasma drug concentration-time curve from time 0 to infinity (AUC0-inf). | Day 1 - Day 85 | 
| Pharmacodynamics of PRX-115: blood uric acid levels | Pharmacodynamics of PRX-115 by measurement of blood uric acid levels over 85 days | Day 0 - Day 85 | 
| Immunogenicity of PRX-115: measurement of anti-drug antibody levels |  | Day 1 - Day 85 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uricase, Gout, Uric acid, PRX-115, hyperuricemia