Study to Assess Pegloticase (KRYSTEXXA®) in Patients on Hemodialysis

Study Overview
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Brief Summary
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This is a Phase 1 single dose study conducted to evaluate the PK and PD of pegloticase administered to hemodialysis patients. A single dose of pegloticase will be administered intravenously to male or female hemodialysis patients (N = 12) starting 3 hour prior to dialysis. The study consists of a Screening Period, a Treatment Period, and Follow up Period.

Detailed Description
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End stage renal disease (ESRD) patients that require hemodialysis typically undergo hemodialysis treatment 3 times per week. As such, medications can be dialyzed off, reducing their clinical effectiveness; this study is being conducted to understand how dialysis affects the pharmacokinetics (PK) and pharmacodynamics (PD) of pegloticase.

Official Title
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A Phase 1, Single Site, Open-Label Study to Assess the Pharmacokinetics (PK) and Pharmacodynamics (PD) of Pegloticase (KRYSTEXXA®) in Patients on Hemodialysis

Conditions
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Chronic Kidney Disease Stage 5

Intervention / Treatment
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* Drug: Pegloticase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 and 75 years of age, inclusive Agrees to employ best possible methods to abstain from becoming pregnant or impregnating another. Stage V chronic kidney patients with minimal or no residual renal function receiving hemodialysis and stable on hemodialysis (3x week) BMI = 18.5 kg/m2 to < 45 kg/m2 Exclusion Criteria: Any surgical or medical condition that may interfere with drug absorption, distribution, metabolism, or excretion, or any other condition that may place the subject at risk Glucose-6-phosphate dehydrogenase (G6PD) deficiency Uncontrolled congestive heart failure Refractory chronic gout History of drug and/or alcohol abuse within 6 months prior to screening History of or current clinically significant mental disorder or an antagonistic personality that compromises the validity of the informed consent Donation of blood or plasma within 30 days prior to dosing History of or current hepatitis, or carriers of hepatitis B surface antigen (HbsAg) and/or hepatitis C antibodies (anti-HC). Use of an investigational drug or product, within 30 days History of clinically significant drug allergies or sensitivities Females with a positive pregnancy test or who are breast feeding at Screening or plan to breast feed within 30 days of dosing A baseline QTc interval ≥ 490 milliseconds for males and ≥ 510 milliseconds for females Is unable to refrain from alcohol Has taken any prescription or over the counter medication within 7 days prior to treatment day that, in the opinion of the Investigator, could be expected to confound the PK or metabolism of the study drug Has taken the following herbal agents or nutraceuticals within 7 days prior to Screening: chapparal, comfrey, germander, gin bu huan, kava, pennyroyal, skullcap, St. John's Wort, or valerian Has poorly controlled malignant hypertension (systolic blood pressure [SBP] > 200 mm Hg and/or diastolic blood pressure [DBP] > 120 mm Hg, Concurrent use of urate-lowering drugs

Ages Eligible for Study
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Minimum Age: 18 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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pegloticase<br>Pegloticase 8 mg single intraveneous dose | Drug: Pegloticase<br>* a single 8 mg iv (in the vein) dose before hemodialysis session<br>* Other names: KRYSTEXXA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • To evaluate the pharmacokinetics (PK) of pegloticase after a single-dose administration to hemodialysis patients when administered starting 3 hours before dialysis |  | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • To evaluate the pharmacodynamics (PD) of pegloticase and SUA, before and after hemodialysis sessions |  | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Kidney Disease Stage 5, Hemodialysis, pegloticase