Purpose

This is a Phase 4, multicenter study of pegloticase in adult participants with uncontrolled gout who have undergone kidney transplantation. Approximately twenty participants will be enrolled. Study duration will be approximately 40 weeks. The purpose of this study is to assess the efficacy and safety of pegloticase in kidney transplant participants with uncontrolled gout refractory to conventional urate lowering therapy.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 GFR (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; and

- 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 (HBV) infection;
  • Known history of hepatitis C virus 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 mmHg) 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.

Study Design

Phase
Phase 4
Study Type
Interventional
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Pegloticase
Participants will receive 8 mg pegloticase by IV infusion every 2 weeks from Day 1 through Week 22
  • Biological: Pegloticase
    Participants will receive 8 mg pegloticase by IV infusion every 2 weeks from Day 1 through Week 22

Recruiting Locations

University of Alabama Birmingham
Birmingham, Alabama 35294
Contact:
Stephanie Clark
205-934-1444
sbiggers@uabmc.edu

More Details

NCT ID
NCT04087720
Status
Recruiting
Sponsor
Horizon Pharma Rheumatology LLC

Study Contact

Jeff Nieves, PharmD
866-479-6742
clinicaltrials@horizontherapeutics.com

Detailed Description

This is a multicenter study of pegloticase in adult participants with uncontrolled gout who have undergone kidney transplantation.

The study design will include: 1) a Screening Period, lasting up to 28 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.