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

Phase 4

Completed

Conditions: Gout
Uncontrolled Gout
Chronic Uncontrolled Gout

Interventions: Biological: Pegloticase with MTX

Registration Number: NCT04511702

Lead Sponsor: Amgen

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 191

Inclusion Criteria

Adult men or women ≥18 years of age.
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
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

Severe chronic or recurrent bacterial infections, such as recurrent pneumonia or chronic bronchiectasis.
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.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency (tested at Screening Visit).
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.
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.
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.
Prior treatment with pegloticase (KRYSTEXXA), another recombinant uricase (rasburicase), or concomitant therapy with a polyethylene glycol-conjugated drug.
Currently receiving systemic or radiologic treatment for ongoing cancer.
History of malignancy within 5 years other than non-melanoma skin cancer or in situ carcinoma of cervix.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Pegloticase 45 Minute Infusion with methotrexate (MTX)	Pegloticase with 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
Pegloticase 60 Minute Infusion with methotrexate (MTX)	Pegloticase with 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
Pegloticase 30 Minute Infusion with methotrexate (MTX)	Pegloticase with 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

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Experienced an Infusion Reaction (IR), Including Anaphylaxis, Related to Pegloticase From Day 1 to Week 24	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Serum Uric Acid (sUA) Responders at Month 6	Up to 6 months	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.
Percentage of Participants Who Experienced an IR Leading to Discontinuation of Treatment, Anaphylaxis or Met sUA Discontinuation Criteria	Day 1 to Week 24	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.
Time to First Event of IR Leading to Discontinuation of Treatment, Anaphylaxis or Meeting sUA Discontinuation Criteria in All Participants	Day 1 to Week 24	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.
Time to First Event of IR Leading to Discontinuation of Treatment, Anaphylaxis or Meeting sUA Discontinuation Criteria in Participants With an Event	Day 1 to Week 24	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.

Trial Locations

Locations (36): Orthopedic Physicians Alaska
🇺🇸
Anchorage, Alaska, United States
D&H Tamarac Research Centers
🇺🇸
Tamarac, Florida, United States
Arthritis & Rheumatology Research
🇺🇸
Mesa, Arizona, United States
Providence Saint John's Health Center
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Santa Monica, California, United States
Bradenton Research Center
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Bradenton, Florida, United States
Prohealth Research Center
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Doral, Florida, United States
MD Medical Research
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Oxon Hill, Maryland, United States
Chattanooga Research & Medicine PLLC (CHARM)
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Chattanooga, Tennessee, United States
Abigail Rebecca Neiman, MD, PA
🇺🇸
Houston, Texas, United States
Velocity Clinical Research Cincinnati
🇺🇸
Cincinnati, Ohio, United States
Arizona Arthritis & Rheumatology Research
🇺🇸
Phoenix, Arizona, United States
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Denver Arthritis Clinic
🇺🇸
Denver, Colorado, United States
Amicis Research Center
🇺🇸
Northridge, California, United States
Medvin Clinical Research
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Tujunga, California, United States
University of Colorado Division of Rheumatology
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Aurora, Colorado, United States
IRIS Research and Development, LLC
🇺🇸
Plantation, Florida, United States
D&H National Research Centers
🇺🇸
Miami, Florida, United States
LIFE Clinical Trials
🇺🇸
Margate, Florida, United States
Napa Research Center
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Pompano Beach, Florida, United States
GCP Clinical Research
🇺🇸
Tampa, Florida, United States
ClinPro Research Solutions
🇺🇸
Tampa, Florida, United States
MedPharmics, LLC
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Metairie, Louisiana, United States
ForCare Clinical Research
🇺🇸
Tampa, Florida, United States
Cape Fear Arthritis Care
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Leland, North Carolina, United States
Santa Fe Rheumatology
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Santa Fe, New Mexico, United States
Long Island Arthritis & Osteoporosis Care
🇺🇸
Babylon, New York, United States
PMG Research of Hickory, LLC
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Hickory, North Carolina, United States
Research Carolina Elite
🇺🇸
Denver, North Carolina, United States
Altoona Center for Clinical Research
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Duncansville, Pennsylvania, United States
PMG Research of Salisbury, LLC
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Salisbury, North Carolina, United States
Shelby Clinical Research, LLC
🇺🇸
Shelby, North Carolina, United States
Pioneer Research Solutions Inc - Houston
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Houston, Texas, United States
Velocity Clinical Research, Salt Lake City
🇺🇸
West Jordan, Utah, United States
Western Washington Medical Group
🇺🇸
Bothell, Washington, United States
Arthritis Northwest
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Spokane, Washington, United States