A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study Assessing the Efficacy, Safety, and Dosing Regimen Selection of Multiple Intravenous Infusions of PRX-115 With and Without Methotrexate Versus Placebo in Adult Patients With Gout (RELEASE)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 35
- 主要终点
- Percentage of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) During Month 6
研究概览
简要总结
This is a multicenter, randomized, double-blind, placebo-controlled phase II study assessing the efficacy, safety, and dosing regimen selection of multiple IV infusions of PRX-115 over 24 weeks, with or without MTX, versus the respective placebos in adult patients with gout.
详细描述
This study will evaluate the efficacy, safety, tolerability, immunogenicity, pharmacokinetics (PK), and pharmacodynamics (PD) of PRX-115 (a recombinant pegylated Uricase) in adult patients with gout. Participants will receive PRX-115 by intravenous (IV) infusions according to different treatment schedules, with and without the immunomodulator methotrexate (MTX).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Males or females ≥18 years of age.
- •Weight within the range of 50.0 - 150.0 kg.
- •Gout patients who failed to normalize sUA (<7 mg/dL) with or without xanthine oxidase inhibitors or uricosuric agent or have contraindications to these drugs.
- •Willing to discontinue any oral ULT
- •Females who are sterile, postmenopausal, or non-pregnant and using birth control methods.
排除标准
- •Any condition known to have arthritis as a clinical manifestation.
- •Positive testing for HBV,HCV, or HIV.
- •The patient is a pregnant or lactating female or plans to become pregnant during the study period.
- •Known allergy or sensitivity to the injected proteins, including pegylated products.
- •Prior exposure to any experimental or marketed uricase.
- •Patient treated with a medication known to have an influence on urate metabolism or clearance such as ULTs.
- •History of anaphylaxis, severe allergic reactions, or severe atopy.
- •G6PD deficiency or known catalase deficiency.
- •History of significant hematologic or autoimmune disorders within 5 years of Screening and/or patient is immunocompromised or treated with immunosuppressive medications.
- •Non-compensated CHF or hospitalization for CHF (Stage 3-4 NYHA Functional Class) within 3 months of the Screening Visit, uncontrolled arrhythmia, treatment for acute coronary syndrome (myocardial infarction or unstable angina), or uncontrolled BP (>160/100 mmHg) at screening and prior to randomization at Week -4 (Visit 1).
- •Current liver disease, as determined by ALT or AST levels above upper limit of normal at Screening Visit.
- •Chronic liver disease.
- •Hemoglobin <11 g/dL, neutrophil count <1500 /µl, or platelet count <100,000 /µl.
- •Known severe pulmonary fibrosis, bronchiectasis or interstitial pneumonitis.
- •eGFR ≤ 40 mL/min/1.73m2 tested at Screening Visit. Kidney transplant or requires dialysis.
- •Known intolerance and/or known contraindication to MTX treatment or MTX treatment considered inappropriate
- •Has uncontrolled type 2 diabetes at Screening with HbA1c ≥8.5%. Patients with type 1 diabetes will be excluded.
- •Has known latent autoimmune diabetes of adult.
- •Immunocompromised state, regardless of etiology.
- •History or treatment of malignancy in the last 5 years, excluding localized, nonmelanoma skin cancers (e.g. basal or squamous cell)
研究组 & 干预措施
E4W with MTX
IV infusion of PRX-115 every 4 weeks (E4W) for a total of 6 doses with MTX
干预措施: PRX-115 (Biological)
E4W with placebo-MTX
IV infusion of PRX-115 every 4 weeks (E4W) for a total of 6 doses with placebo-MTX
干预措施: Placebo-Methotrexate (Other)
E4W with placebo-MTX
IV infusion of PRX-115 every 4 weeks (E4W) for a total of 6 doses with placebo-MTX
干预措施: PRX-115 (Biological)
placebo E6W
IV infusion of PRX-115 placebo every 6 weeks (E6W) for a total of 4 doses with placebo-MTX
干预措施: PRX-115 placebo (Other)
E8W with MTX
IV infusion of PRX-115 every 8 weeks (E8W) for a total of 3 doses with MTX
干预措施: PRX-115 (Biological)
E6W with MTX
IV infusion of PRX-115 every 6 weeks (E6W) for a total of 4 doses with MTX
干预措施: Methotrexate (MTX) (Drug)
E8W with MTX
IV infusion of PRX-115 every 8 weeks (E8W) for a total of 3 doses with MTX
干预措施: Methotrexate (MTX) (Drug)
placebo E6W
IV infusion of PRX-115 placebo every 6 weeks (E6W) for a total of 4 doses with placebo-MTX
干预措施: Placebo-Methotrexate (Other)
placebo E4W
infusion of PRX-115 placebo every 4 weeks (E4W) for a total of 6 doses with placebo-MTX
干预措施: PRX-115 placebo (Other)
placebo E4W
infusion of PRX-115 placebo every 4 weeks (E4W) for a total of 6 doses with placebo-MTX
干预措施: Placebo-Methotrexate (Other)
E4W with MTX
IV infusion of PRX-115 every 4 weeks (E4W) for a total of 6 doses with MTX
干预措施: Methotrexate (MTX) (Drug)
E6W with MTX
IV infusion of PRX-115 every 6 weeks (E6W) for a total of 4 doses with MTX
干预措施: PRX-115 (Biological)
结局指标
主要结局
Percentage of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) During Month 6
时间窗: 6 months of treatment
Proportion of patients who achieve a reduction in sUA to \<6.0 mg/dL for at least 80% of the time during Month 6
次要结局
- Treatment-emergent adverse events (TEAEs)(From enrollment to 8 months of study)
- Percentage of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) at different time points(3 to 6 months of treatment)