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
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 191
- 试验地点
- 36
- 主要终点
- Percentage of Participants Who Experienced an Infusion Reaction (IR), Including Anaphylaxis, Related to Pegloticase From Day 1 to Week 24
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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 -
- •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.
研究组 & 干预措施
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
干预措施: Pegloticase with MTX (Biological)
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
干预措施: Pegloticase with MTX (Biological)
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
干预措施: Pegloticase with MTX (Biological)
结局指标
主要结局
Percentage of Participants Who Experienced an Infusion Reaction (IR), Including Anaphylaxis, Related to Pegloticase From Day 1 to Week 24
时间窗: 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.
次要结局
- Percentage of Serum Uric Acid (sUA) Responders at Month 6(Up to 6 months)
- Percentage of Participants Who Experienced an IR Leading to Discontinuation of Treatment, Anaphylaxis or Met sUA Discontinuation Criteria(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(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(Day 1 to Week 24)