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

NCT ID: NCT04087720

Last Updated: 2024-06-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-09
• Study Completion Date: 2021-09-07

Brief Summary

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

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.

Study acquired from Horizon in 2024.

Conditions

Uncontrolled Gout; Kidney Transplant

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pegloticase

Participants receive 8 mg pegloticase every 2 weeks from Day 1 through Week 22

Group Type: EXPERIMENTAL

Pegloticase

Intervention Type: BIOLOGICAL

intravenous (IV) infusion

Interventions

Pegloticase

intravenous (IV) infusion

Intervention Type: BIOLOGICAL

Eligibility Criteria

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:

1. 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

2. Inability to maintain sUA <6 mg/dL on other urate-lowering therapy or intolerable side effects or contraindicated with conventional urate-lowering therapy, and

3. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

University of Alabama Birmingham

Birmingham, Alabama, United States

Nephrology Consultants

Huntsville, Alabama, United States

Keck School of Medicine of USC

Los Angeles, California, United States

Amicis Research Center

Northridge, California, United States

Genesis Clinical Research

Tampa, Florida, United States

Coastal Medical Research

Brunswick, Georgia, United States

Duke University Medical Center

Durham, North Carolina, United States

Clear Lake Specialties

Webster, Texas, United States

Countries

United States

References

Dalbeth N, Abdellatif A, Botson JK, Saag KG, Kumar A, Padnick-Silver L, Vranic Z, Marder BA, Becce F. Monosodium Urate Crystal Depletion and Bone Erosion Response in Kidney Transplant Recipients With Uncontrolled Gout Treated With Pegloticase: PROTECT Serial Dual-Energy Computed Tomography Findings. Transplant Direct. 2025 May 12;11(6):e1803. doi: 10.1097/TXD.0000000000001803. eCollection 2025 Jun.

Reference Type: DERIVED

PMID: 40371056 (View on PubMed)

Abdellatif A, Zhao L, Chamberlain J, Cherny K, Xin Y, Marder BA, Scandling JD, Saag K. Pegloticase efficacy and safety in kidney transplant recipients; results of the phase IV, open-label PROTECT clinical trial. Clin Transplant. 2023 Sep;37(9):e14993. doi: 10.1111/ctr.14993. Epub 2023 May 3.

Reference Type: DERIVED

PMID: 37138473 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

HZNP-KRY-406

Identifier Type: -

Identifier Source: org_study_id