Infusion Duration Study To Assess Tolerability of Pegloticase Administered With a Shorter Infusion Duration in Subjects With Uncontrolled Gout Receiving Methotrexate

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

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.

Study Overview

• Status: Completed
• Conditions: Gout; Chronic Uncontrolled Gout; Uncontrolled Gout
• Intervention / Treatment: Biological: Pegloticase with MTX

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.

• Study Type: Interventional
• Enrollment (Actual): 191
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Orthopedic Physicians Alaska
  • Arizona
    • Gilbert, Arizona, United States, 85297
      • Arizona Arthritis & Rheumatology Research
    • Mesa, Arizona, United States, 85210
      • Arthritis & Rheumatology Research
    • Phoenix, Arizona, United States, 85037
      • Arizona Arthritis & Rheumatology Research
  • California
    • Covina, California, United States, 91722
      • Medvin Clinical Research
    • Northridge, California, United States, 91324
      • Amicis Research Center
    • Santa Monica, California, United States, 90404
      • Providence Saint John's Health Center
    • Thousand Oaks, California, United States, 91360
      • Medvin Clinical Research
    • Tujunga, California, United States, 91042
      • Medvin Clinical Research
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Division of Rheumatology
    • Denver, Colorado, United States, 80230
      • Denver Arthritis Clinic
  • Florida
    • Bradenton, Florida, United States, 34205
      • Bradenton Research Center
    • Doral, Florida, United States, 33166
      • Prohealth Research Center
    • Margate, Florida, United States, 33063
      • LIFE Clinical Trials
    • Miami, Florida, United States, 33155
      • D&H National Research Centers
    • Plantation, Florida, United States, 33324
      • IRIS Research and Development, LLC
    • Pompano Beach, Florida, United States, 33064
      • Napa Research Center
    • Tamarac, Florida, United States, 33321
      • D&H Tamarac Research Centers
    • Tampa, Florida, United States, 33613
      • ForCare Clinical Research
    • Tampa, Florida, United States, 33064
      • GCP Clinical Research
    • Tampa, Florida, United States, 33609
      • ClinPro Research Solutions
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • MedPharmics, LLC
  • Maryland
    • Oxon Hill, Maryland, United States, 20745
      • MD Medical Research
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Santa Fe Rheumatology
  • New York
    • Babylon, New York, United States, 11702
      • Long Island Arthritis & Osteoporosis Care
  • North Carolina
    • Denver, North Carolina, United States, 28037
      • Research Carolina Elite
    • Hickory, North Carolina, United States, 28602
      • PMG Research of Hickory, LLC
    • Leland, North Carolina, United States, 28451
      • Cape Fear Arthritis Care
    • Salisbury, North Carolina, United States, 28144
      • PMG Research of Salisbury, LLC
    • Shelby, North Carolina, United States, 28150
      • Shelby Clinical Research, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Velocity Clinical Research Cincinnati
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center For Clinical Research
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Research & Medicine PLLC (CHARM)
  • Texas
    • Houston, Texas, United States, 77024
      • Abigail Rebecca Neiman, MD, PA
    • Houston, Texas, United States, 77099
      • Pioneer Research Solutions Inc - Houston
  • Utah
    • West Jordan, Utah, United States, 84088
      • Velocity Clinical Research, Salt Lake City
  • Washington
    • Bothell, Washington, United States, 98021
      • Western Washington Medical Group
    • Spokane, Washington, United States, 99204
      • Arthritis Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pegloticase 60 Minute Infusion with methotrexate (MTX); Pegloticase 60 Minute Infusion with methotrexate (MTX). Participants will receive MTX (15 mg) (weekly) during the Run-in Period, then pegloticase (every 2 weeks) with MTX (weekly) for 24 weeks	Biological: Pegloticase with MTX; Participants will receive MTX during the run-in period then pegloticase with MTX for up to 24 weeks during the treatment period; Other Names: Methotrexate
Experimental: Pegloticase 45 Minute Infusion with methotrexate (MTX); Pegloticase 45 Minute Infusion with methotrexate (MTX). Participants will receive MTX (15 mg) (weekly) during the Run-in Period, then pegloticase (every 2 weeks) with MTX (weekly) for 24 weeks	Biological: Pegloticase with MTX; Participants will receive MTX during the run-in period then pegloticase with MTX for up to 24 weeks during the treatment period; Other Names: Methotrexate
Experimental: Pegloticase 30 Minute Infusion with methotrexate (MTX); Pegloticase 30 Minute Infusion with methotrexate (MTX). Participants will receive MTX (15 mg) (weekly) during the Run-in Period, then pegloticase (every 2 weeks) with MTX (weekly) for 24 weeks	Biological: Pegloticase with MTX; Participants will receive MTX during the run-in period then pegloticase with MTX for up to 24 weeks during the treatment period; Other Names: Methotrexate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experienced an Infusion Reaction (IR), Including Anaphylaxis, Related to Pegloticase From Day 1 to Week 24	IRs, including anaphylaxis, were assessed after each infusion for a period of 24 weeks. IRs were defined as any infusion-related adverse event (AE) or cluster of temporally-related AEs, not attributable to another cause, which occurred during the pegloticase infusion and up to 2 hours post-infusion. Additional AEs occurring outside of the 2-hour window following infusion could also be categorized as an IR at the Principal Investigator's discretion.	Day 1 to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Serum Uric Acid (sUA) Responders at Month 6	Responders were defined as participants who achieved and maintained sUA levels below 6 mg/dL for at least 80% of the time during month 6. Responders who met sUA discontinuation criteria (2 consecutive sUA > 6 mg/dL), regardless of treatment status were considered non-responders.	Up to 6 months
Percentage of Participants Who Experienced an IR Leading to Discontinuation of Treatment, Anaphylaxis or Met sUA Discontinuation Criteria	IRs were defined as any infusion-related AE or cluster of temporally-related AEs, not attributable to another cause, which occurred during the pegloticase infusion and for 2 hours post-infusion. Other AEs that occurred outside of the 2 hour window following the infusion may have also been categorized as an IR at the Principal Investigator's discretion. Anaphylaxis was defined using the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network criteria. Meeting individual sUA discontinuation criteria was defined as two consecutive pre-infusion sUAs > 6 mg/dL after Day 1.	Day 1 to Week 24
Time to First Event of IR Leading to Discontinuation of Treatment, Anaphylaxis or Meeting sUA Discontinuation Criteria in All Participants	Infusion reactions were defined as any infusion-related adverse event or cluster of temporally-related adverse events, not attributable to another cause, which occurred during the infusion and for 2 hours post-infusion. Other adverse events that occurred outside of the 2-hour window following the infusion may have also been categorized as an infusion reaction at the Principal Investigator's discretion. Anaphylaxis was defined using the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network criteria. Meeting individual serum uric acid discontinuation criteria was defined as two consecutive pre-infusion serum uric acid levels greater than 6 mg/dL after Day 1. Time to event was derived as the date of the event minus the date of the first dose of the treatment plus 1. All participants were censored at the date of their last infusion.	Day 1 to Week 24
Time to First Event of IR Leading to Discontinuation of Treatment, Anaphylaxis or Meeting sUA Discontinuation Criteria in Participants With an Event	IRs were defined as any infusion-related adverse event or cluster of temporally-related adverse events, not attributable to another cause, which occurred during the infusion and for 2 hours post-infusion. Other adverse events that occurred outside of the 2-hour window following the infusion may have also been categorized as an infusion reaction at the Principal Investigator's discretion. Anaphylaxis was defined using the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network criteria. Meeting individual serum uric acid discontinuation criteria was defined as two consecutive pre-infusion serum uric acid levels greater than 6 mg/dL after Day 1. Time to event was derived as the date of the event minus the date of the first dose of the treatment plus 1. Only participants who experienced an event were included in this analysis.	Day 1 to Week 24

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2020
• Primary Completion (Actual): January 18, 2024
• Study Completion (Actual): March 25, 2024

Study Registration Dates

• First Submitted: August 11, 2020
• First Submitted That Met QC Criteria: August 11, 2020
• First Posted (Actual): August 13, 2020

Study Record Updates

• Last Update Posted (Actual): October 20, 2025
• Last Update Submitted That Met QC Criteria: October 7, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: gout; uncontrolled gout
• Additional Relevant MeSH Terms: Crystal Arthropathies; Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Gout; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pterins; Pteridines; Aminopterin; Methotrexate; Pegloticase
• Other Study ID Numbers: HZNP-KRY-403

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No