Study of Pegloticase in Participants With Uncontrolled Gout Who Have Had a Kidney Transplant

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the effect of pegloticase on the response rate of sustained serum uric acid (sUA) reduction to sUA < 6 mg/dL during Month 6 of treatment.

Detailed Description
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The study design includes: 1) a Screening Period, lasting up to 35 days; 2) a 24-week treatment period which includes an End-of-Study (Week 24) /Early Termination Visit; 3) a safety follow-up phone/email Visit 30 days after the last infusion; and 4) a 3 month post-treatment follow up visit.

Official Title
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A Multicenter, Open-Label, Efficacy and Safety Study of Pegloticase in Patients With Uncontrolled Gout Who Have Undergone Kidney Transplantation

Conditions
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Uncontrolled Gout, Kidney Transplant

Intervention / Treatment
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* Biological: Pegloticase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to give informed consent; Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the study; Adult men or women ≥ 18 years of age; Is a recipient of a de novo kidney from a living or deceased donor and is >1 year post transplant prior to screening; Is on a stable standard of care immunosuppression therapy for at least 3 months prior to screening; Kidney allograft is functional at entry, based on an estimated glomerular filtration rate (eGFR) ≥ 15 mL/min/1.73m²; Women of childbearing potential have a negative screening serum pregnancy test and will be required to use a medically approved form of birth control during their participation in the study; Uncontrolled gout, defined as: Hyperuricemia during screening as documented by sUA ≥ 7 mg/dL during Screening and prior to entry into the Treatment Period (Note: the sUA may be repeated up to 3 times during the Screening Period to confirm eligibility), and Inability to maintain sUA <6 mg/dL on other urate-lowering therapy or intolerable side effects or contraindicated with conventional urate-lowering therapy, and At least 1 of the following: i. Evidence of tophaceous deposits; ii. Recurrent gout flares defined as 2 or more flares in the 12 months prior to Screening; iii. Presence of chronic gouty arthritis; Able to tolerate low-dose prednisone (< 10 mg/day) as part of the required standard gout flare prophylaxis regimen for ≥ 1 week before the first infusion. Exclusion Criteria: Any other organ transplant beside kidney; Any severe infection, unless treated and completely resolved at least 2 weeks prior to Day 1; Chronic or active hepatitis B virus infection; Known history of hepatitis C virus ribonucleic acid (RNA) positivity unless treated and viral load is negative; Known history of human immunodeficiency virus (HIV) positivity; Glucose-6-phosphate dehydrogenase (G6PD) deficiency (tested at the Screening Visit); Decompensated congestive heart failure or hospitalization for congestive heart failure within 3 months of the Screening Visit, uncontrolled arrhythmia, treatment for acute coronary syndrome (myocardial infarction or unstable angina), or uncontrolled blood pressure (> 160/100 mm Hg) at the end of the Screening Period (Day 1 prior to infusion); Pregnant, planning to become pregnant, breastfeeding, planning to impregnate female partner, or not using an effective form of birth control, as determined by the Investigator; Prior treatment with pegloticase, another recombinant uricase (rasburicase), or concomitant therapy with a polyethylene glycol-conjugated drug; Known allergy to pegylated products or history of anaphylactic reaction to a recombinant protein or porcine product; Receipt of an investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to Day 1, or plans to take an investigational drug during the study; Currently receiving systemic or radiologic treatment for ongoing cancer; History of malignancy within 5 years other than non-melanoma skin cancer, in situ carcinoma of cervix, early stage renal cell cancer or early stage prostate cancer that has been completely resected > 2 years prior to screening; Uncontrolled hyperglycemia with a plasma glucose value > 240 mg/dL at Screening that is not subsequently controlled by the end of the Screening Period; Diagnosis of osteomyelitis; Known history of hypoxanthine-guanine phosphoribosyl-transferase deficiency, such as Lesch-Nyhan and Kelley-Seegmiller syndrome; Unsuitable candidate for the study, based on the opinion of the Investigator (e.g., cognitive impairment), such that participation might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements or complete the study; Currently receiving allopurinol, febuxostat or other urate lowering medications and unable to discontinue medication 7 days prior to Day 1; or Currently receiving probenecid and unable to discontinue medication within 3 days, prior to Day 1.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pegloticase<br>Participants receive 8 mg pegloticase every 2 weeks from Day 1 through Week 22 | Biological: Pegloticase<br>* intravenous (IV) infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Serum Uric Acid (sUA) < 6 mg/dL Responders During Month 6 | sUA < 6 mg/dL responders are defined as participants achieving and maintaining sUA < 6 mg/dL for at least 80% of the time during Month 6, which includes pre-infusion and post-infusion results at Week 20, results at Week 21, pre-infusion and post-infusion results at Week 22, results at Week 23, results at Week 24, and unscheduled assessments of sUA collected between Week 20 and Week 24. Two-sided Exact Clopper-Pearson confidence interval is used for the calculation of the 95% confidence interval. | Month 6 (Weeks 20, 21, 22, 23, 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of sUA < 5 mg/dL Responders During Month 6 | sUA < 5 mg/dL responders are defined as participants achieving and maintaining sUA <5 mg/dL for at least 80% of the time during Month 6, which includes pre-infusion and post-infusion results at Week 20, results at Week 21, pre-infusion and post-infusion results at Week 22, results at Week 23, results at Week 24, and unscheduled assessments of sUA collected between Week 20 and Week 24. Two-sided Exact Clopper-Pearson confidence interval is used for the calculation of the 95% confidence interval. | Month 6 (Weeks 20, 21, 22, 23, and 24) | 
| Change From Baseline in Health Assessment Questionnaire (HAQ) Pain Visual Analog Scale (VAS) Score Through Week 24 | The HAQ-Pain score consists of a doubly anchored, horizontal VAS 15 cm in length, and rates a participant's pain over the past week from 0 to 100 with 0 = no pain and 100 = severe pain. Baseline is defined as the last measurement taken prior to the first infusion of pegloticase. The 95% confidence interval is a two-sided normal theory-based 95% confidence interval. | Baseline, Weeks 6, 14, 20, 24 | 
| Change From Baseline in Heath Assessment Questionnaire - Disability Index (HAQ-DI) Score Through Week 24 | The HAQ-DI is a self-reported assessment of how a participant's illness affects their ability to function in their daily life over the past week. The HAQ-DI for a participant is calculated as the mean of the following 8 category scores: Dressing and Grooming, Arising, Eating, Walking, Hygiene, Reach, Grip, and Activities. The HAQ-DI ranges from 0 to 3 with higher values indicating higher disability. Baseline is defined as the last measurement taken prior to the first infusion of pegloticase. The 95% confidence interval is a two-sided normal theory-based 95% confidence interval. | Baseline, Weeks 6, 14, 20, 24 |