A Double-blind, Randomized Controlled Trial to Investigate the Efficacy, Safety, and Pharmacokinetics of Pegloticase Administration Via Subcutaneous and Intravenous Routes Both With Methotrexate in Participants With Uncontrolled Gout

A Phase 3, Multicenter, Double-blind, Randomized Controlled Study Evaluating the Efficacy and Safety of Pegloticase Administered by Subcutaneous Injection Compared With Pegloticase Administered by Intravenous Injection, Both Administered Concurrently With Methotrexate Weekly, in Participants With Uncontrolled Gout

The primary objective of this trial is to evaluate the effect of pegloticase 18 mg subcutaneously (SC) every two weeks with methotrexate (MTX) versus pegloticase 8 mg intravenously (IV) every two weeks with MTX on the response rate during Month 6, as measured by the sustained normalization of serum uric acid (sUA) to < 6 mg/dL for at least 80% of the time during Month 6.

Study Overview

• Status: Recruiting
• Conditions: Uncontrolled Gout
• Intervention / Treatment: Drug: Pegloticase; Drug: Methotrexate

• Study Type: Interventional
• Enrollment (Estimated): 270
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Amgen Call Center; Phone Number: 866-572-6436; Email: medinfo@amgen.com

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00917
    • Recruiting
    • Caribbean Health Research Center
• United States
  • California
    • Tustin, California, United States, 92780
      • Recruiting
      • Solace Clinical Research
  • Colorado
    • Denver, Colorado, United States, 80230
      • Recruiting
      • Denver Arthritis Clinic PC
  • Florida
    • Aventura, Florida, United States, 33180
      • Recruiting
      • D and H Pompano Research Center
    • Hialeah, Florida, United States, 33016
      • Recruiting
      • New Generation of Medical Research
    • Homestead, Florida, United States, 33033
      • Recruiting
      • Homestead Associates in Research Inc
    • Miami, Florida, United States, 33156
      • Recruiting
      • Advanced Clinical Research
    • Miami, Florida, United States, 33184
      • Recruiting
      • Felicidad Medical Research
    • Miami, Florida, United States, 33155
      • Recruiting
      • D and H National Research Centers
    • Miami, Florida, United States, 33143
      • Recruiting
      • Well Pharma Medical Research Corp
    • Pinellas Park, Florida, United States, 33782
      • Recruiting
      • Decision Management International Research
    • Plantation, Florida, United States, 33324
      • Recruiting
      • Integral Rheumatology And Immunology Specialists
    • Tamarac, Florida, United States, 33321
      • Recruiting
      • D and H Tamarac Research Center
    • Tampa, Florida, United States, 33609
      • Recruiting
      • GCP Clinical Research, LLC
    • Tampa, Florida, United States, 33613
      • Recruiting
      • ClinPro Research Solutions LLC
    • Winter Park, Florida, United States, 32789
      • Recruiting
      • Conquest Research - Winter Park
  • Georgia
    • Marietta, Georgia, United States, 30066
      • Recruiting
      • Spatium Urgent Care
    • Newnan, Georgia, United States, 30265
      • Recruiting
      • Vista Clinical Research
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Recruiting
      • Flourish Research Ravenswood
    • Chicago, Illinois, United States, 60618
      • Recruiting
      • Charter Research
    • Schaumburg, Illinois, United States, 60195
      • Recruiting
      • Greater Chicago Specialty Physicians
    • Willowbrook, Illinois, United States, 60527
      • Recruiting
      • Willow Rheumatology and Wellness
  • Maryland
    • Columbia, Maryland, United States, 21045
      • Recruiting
      • Kur Research at Columbia Medical Practice
    • Oxon Hill, Maryland, United States, 20745
      • Recruiting
      • MD Medical Research
  • New York
    • Orchard Park, New York, United States, 14127
      • Recruiting
      • Buffalo Rheumatology and Medicine
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Joint and Muscle Research Institute
    • Leland, North Carolina, United States, 28451
      • Recruiting
      • Cape Fear Arthritis Care, PLLC
    • Salisbury, North Carolina, United States, 28144
      • Recruiting
      • Accellacare Salisbury
    • Shelby, North Carolina, United States, 28150
      • Recruiting
      • Shelby Clinical Research
    • Shelby, North Carolina, United States, 28150
      • Recruiting
      • Carolina Research Center Inc
  • Ohio
    • Middleburg Heights, Ohio, United States, 44130
      • Recruiting
      • Paramount Medical Research and Consulting LLC
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Recruiting
      • Altoona Center For Clinical Research
  • South Carolina
    • Summerville, South Carolina, United States, 29486
      • Recruiting
      • Articularis Healthcare Group Inc dba Low Country Rheumatology
  • Texas
    • Houston, Texas, United States, 77099
      • Recruiting
      • Pioneer Research Solutions Inc
    • Lewisville, Texas, United States, 75057
      • Recruiting
      • Epic Clinical Research
    • Round Rock, Texas, United States, 78681
      • Recruiting
      • Be Well Clinical Studies
  • Washington
    • Bellevue, Washington, United States, 98004
      • Recruiting
      • Overlake Arthritis and Osteoperosis Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Participant has provided informed consent before initiation of any trial-specific activities/procedures.
• Age ≥ 18 years or ≥ legal age within the country if it is older than 18 years.
• Participants willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.
• Participants with uncontrolled gout, as meeting the protocol defined criteria.

Exclusion Criteria

• Glucose-6-phosphate dehydrogenase deficiency (tested at the screening visit).
• Liver transaminase levels (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) > 1.25 x upper limit of normal (ULN) or albumin < the lower limit of normal (LLN) at the screening visit.
• Uncontrolled diabetes mellitus and/or hemoglobin A1c (HbA1c) > 8%.
• Known intolerance to MTX.
• Participant received prior treatment with pegloticase, another recombinant uricase (ie, rasburicase or pegadricase), or concomitant therapy with a polyethylene glycol (PEG)-conjugated drug.
• A known intolerance to all protocol standard gout flare prophylaxis regimens (ie, participant must be able to tolerate at least 1 of the following: colchicine and/or non-steroidal anti-inflammatory drug and/or low-dose prednisone ≤ 10 mg/day or equivalent dose of other corticosteroid).
• Chronic renal impairment defined as estimated glomerular filtration rate (eGFR) based on Modification of Diet in Renal Disease (MDRD) calculations < 40 mL/min/1.73 m^2 or currently on dialysis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pegloticase SC with MTX; Participants will receive pegloticase SC every two weeks with MTX.	Drug: Pegloticase; Participants will receive pegloticase either SC or IV.; Other Names: KRYSTEXXA; Drug: Methotrexate; MTX will be administered orally.; Other Names: MTX
Experimental: Pegloticase IV with MTX; Participants will receive pegloticase IV every two weeks with MTX.	Drug: Pegloticase; Participants will receive pegloticase either SC or IV.; Other Names: KRYSTEXXA; Drug: Methotrexate; MTX will be administered orally.; Other Names: MTX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Achieving Month 6 Response at Weeks 20, 21, 22, 23, and 24	Defined as Achieving and Maintaining sUA < 6 mg/dL for at Least 80% of the Time During Month 6.	Month 6 (Weeks 20, 21, 22, 23, and 24)

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Serious Injection Site Reactions Through Week 48	Up to Week 48
Number of Participants With Serious Adjudicated Infusion Reactions (Including Adjudicated Anaphylaxis) Through Week 48	Up to Week 48
Number of Participants With Adjudicated Anaphylaxis Through Week 48	Up to Week 48
Serum Concentrations of Pegloticase Following SC and IV Administration	Up to Week 48

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): February 9, 2026
• Primary Completion (Estimated): May 23, 2028
• Study Completion (Estimated): July 18, 2028

Study Registration Dates

• First Submitted: January 29, 2026
• First Submitted That Met QC Criteria: January 29, 2026
• First Posted (Actual): February 5, 2026

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: KRYSTEXXA; Pegloticase; Uncontrolled Gout; Kadence
• Additional Relevant MeSH Terms: Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pterins; Pteridines; Aminopterin; Methotrexate; Pegloticase
• Other Study ID Numbers: 20230219

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• 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 trial will be considered beginning 18 months after the trial has ended and either 1) the product and indication (or other new use) 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 trial.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen trial/trials 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, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. 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