Clinical trial NCT04511702: Infusion Duration Study To Assess Tolerability of Pegloticase Administered With a Shorter Infusion Duration in Subjects With Uncontrolled Gout Receiving Methotrexate
Official title: A Phase 4, Multicenter, Open-Label, Infusion Duration Study To Assess Safety, Tolerability and Efficacy of Pegloticase Administered With a Shorter Infusion Duration in Subjects With Uncontrolled Gout Receiving Methotrexate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Uncontrolled Gout
Gout
Uncontrolled Gout
Keywords: gout
uncontrolled gout
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2020-08-13
Enrollment: 191
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Three different infusion durations may be used. 60-minute infusion, 45-minute infusion and 30-minute.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety, tolerability and efficiency of pegloticase administered with a shorter infusion duration in participants with uncontrolled gout receiving methotrexate.

Detailed description: Approximately 180 participants will be enrolled. After a 4-week methotrexate run-in period, participants will be treated for up to 24 weeks with weekly oral methotrexate and biweekly 8mg pegloticase infusions. Up to three pegloticase infusion durations will be assessed in the study: 60-minute infusion, 45-minute infusion and 30-minute infusion. Safety evaluations will be performed regularly throughout the course of the study.

Acquired from Horizon in 2024.

Eligibility criteria: Inclusion Criteria:

1. Adult men or women ≥18 years of age.
2. Uncontrolled gout, defined as meeting the following criteria:

   * Hyperuricemia during the screening period defined as sUA ≥6 mg/dL
   * Failure to maintain normalization of sUA with xanthine oxidase inhibitors at the maximum medically appropriate dose, or with intolerable side effects or a contraindication to xanthine oxidase inhibitor therapy based on medical record review or subject interview.
   * Symptoms of gout including at least 1 of the following:

     * Presence of at least one tophus
     * Recurrent flares defined as 2 or more flares in the past 12 months prior to screening
     * Presence of chronic gouty arthritis
3. Willing to discontinue all oral urate-lowering therapy at least 7 days prior to MTX dosing at Week -4 and remain off of urate lowering therapy when receiving pegloticase infusions during the study.

Exclusion Criteria:

1. Severe chronic or recurrent bacterial infections, such as recurrent pneumonia or chronic bronchiectasis.
2. Current or chronic treatment with systemic immunosuppressive agents such as MTX, azathioprine, or mycophenolate mofetil; prednisone ≥10 mg/day or equivalent dose of other corticosteroid on a chronic basis (defined as 3 months or longer) would also meet exclusion criteria.
3. Glucose-6-phosphate dehydrogenase (G6PD) deficiency (tested at Screening Visit).
4. Severe chronic renal impairment (estimated glomerular filtration rate \<40 mL/min/1.73 m2) at the Screening Visit based on 4 variable-Modification of Diet in Renal Disease \[MDRD\] formula or currently on dialysis.
5. Non-compensated congestive heart failure or hospitalization for congestive heart failure or treatment for acute coronary syndrome (myocardial infarction or unstable angina) within 3 months of the Screening Visit, or current uncontrolled arrhythmia, or current uncontrolled blood pressure (BP) (\>160/100 mmHg) prior to Week -4.
6. Pregnant, planning to become pregnant, breastfeeding, planning to impregnate female partner, or not on an effective form of birth control, as determined by the Investigator.
7. Prior treatment with pegloticase (KRYSTEXXA), another recombinant uricase (rasburicase), or concomitant therapy with a polyethylene glycol-conjugated drug.
8. Currently receiving systemic or radiologic treatment for ongoing cancer.
9. History of malignancy within 5 years other than non-melanoma skin cancer or in situ carcinoma of cervix.

Primary outcomes:
measure: Percentage of Participants Who Experienced an Infusion Reaction (IR), Including Anaphylaxis, Related to Pegloticase From Day 1 to Week 24
timeFrame: Day 1 to Week 24
Secondary outcomes:
measure: Percentage of Serum Uric Acid (sUA) Responders at Month 6
timeFrame: Up to 6 months
measure: Percentage of Participants Who Experienced an IR Leading to Discontinuation of Treatment, Anaphylaxis or Met sUA Discontinuation Criteria
timeFrame: Day 1 to Week 24
measure: Time to First Event of IR Leading to Discontinuation of Treatment, Anaphylaxis or Meeting sUA Discontinuation Criteria in All Participants
timeFrame: Day 1 to Week 24
measure: Time to First Event of IR Leading to Discontinuation of Treatment, Anaphylaxis or Meeting sUA Discontinuation Criteria in Participants With an Event
timeFrame: Day 1 to Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Anchorage
country: United States
facility: Orthopedic Physicians Alaska
state: Alaska
city: Gilbert
country: United States
facility: Arizona Arthritis & Rheumatology Research
state: Arizona
city: Mesa
country: United States
facility: Arthritis & Rheumatology Research
state: Arizona
city: Phoenix
country: United States
facility: Arizona Arthritis & Rheumatology Research
state: Arizona
city: Covina
country: United States
facility: Medvin Clinical Research
state: California
city: Northridge
country: United States
facility: Amicis Research Center
state: California
city: Santa Monica
country: United States
facility: Providence Saint John's Health Center
state: California
city: Thousand Oaks
country: United States
facility: Medvin Clinical Research
state: California
city: Tujunga
country: United States
facility: Medvin Clinical Research
state: California
city: Aurora
country: United States
facility: University of Colorado Division of Rheumatology
state: Colorado
city: Denver
country: United States
facility: Denver Arthritis Clinic
state: Colorado
city: Bradenton
country: United States
facility: Bradenton Research Center
state: Florida
city: Doral
country: United States
facility: Prohealth Research Center
state: Florida
city: Margate
country: United States
facility: LIFE Clinical Trials
state: Florida
city: Miami
country: United States
facility: D&H National Research Centers
state: Florida
city: Plantation
country: United States
facility: IRIS Research and Development, LLC
state: Florida
city: Pompano Beach
country: United States
facility: Napa Research Center
state: Florida
city: Tamarac
country: United States
facility: D&H Tamarac Research Centers
state: Florida
city: Tampa
country: United States
facility: GCP Clinical Research
state: Florida
city: Tampa
country: United States
facility: ClinPro Research Solutions
state: Florida
city: Tampa
country: United States
facility: ForCare Clinical Research
state: Florida
city: Metairie
country: United States
facility: MedPharmics, LLC
state: Louisiana
city: Oxon Hill
country: United States
facility: MD Medical Research
state: Maryland
city: Santa Fe
country: United States
facility: Santa Fe Rheumatology
state: New Mexico
city: Babylon
country: United States
facility: Long Island Arthritis & Osteoporosis Care
state: New York
city: Denver
country: United States
facility: Research Carolina Elite
state: North Carolina
city: Hickory
country: United States
facility: PMG Research of Hickory, LLC
state: North Carolina
city: Leland
country: United States
facility: Cape Fear Arthritis Care
state: North Carolina
city: Salisbury
country: United States
facility: PMG Research of Salisbury, LLC
state: North Carolina
city: Shelby
country: United States
facility: Shelby Clinical Research, LLC
state: North Carolina
city: Cincinnati
country: United States
facility: Velocity Clinical Research Cincinnati
state: Ohio
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Chattanooga
country: United States
facility: Chattanooga Research & Medicine PLLC (CHARM)
state: Tennessee
city: Houston
country: United States
facility: Abigail Rebecca Neiman, MD, PA
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions Inc - Houston
state: Texas
city: West Jordan
country: United States
facility: Velocity Clinical Research, Salt Lake City
state: Utah
city: Bothell
country: United States
facility: Western Washington Medical Group
state: Washington
city: Spokane
country: United States
facility: Arthritis Northwest
state: Washington
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: