Clinical trial NCT04087720: Study of Pegloticase in Participants With Uncontrolled Gout Who Have Had a Kidney Transplant
Official title: A Multicenter, Open-Label, Efficacy and Safety Study of Pegloticase in Patients With Uncontrolled Gout Who Have Undergone Kidney Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Uncontrolled Gout
Kidney Transplant
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2019-09-12
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage of Serum Uric Acid (sUA) < 6 mg/dL Responders During Month 6
timeFrame: Month 6 (Weeks 20, 21, 22, 23, 24)
Secondary outcomes:
measure: Percentage of sUA < 5 mg/dL Responders During Month 6
timeFrame: Month 6 (Weeks 20, 21, 22, 23, and 24)
measure: Change From Baseline in Health Assessment Questionnaire (HAQ) Pain Visual Analog Scale (VAS) Score Through Week 24
timeFrame: Baseline, Weeks 6, 14, 20, 24
measure: Change From Baseline in Heath Assessment Questionnaire - Disability Index (HAQ-DI) Score Through Week 24
timeFrame: Baseline, Weeks 6, 14, 20, 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: Huntsville
country: United States
facility: Nephrology Consultants
state: Alabama
city: Los Angeles
country: United States
facility: Keck School of Medicine of USC
state: California
city: Northridge
country: United States
facility: Amicis Research Center
state: California
city: Tampa
country: United States
facility: Genesis Clinical Research
state: Florida
city: Brunswick
country: United States
facility: Coastal Medical Research
state: Georgia
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Webster
country: United States
facility: Clear Lake Specialties
state: Texas
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: