A Double-blind, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Properties of PRX-115 in Adult Volunteers with Elevated Uric Acid Levels.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Number of participants with adverse events receiving PRX-115 compared to placebo
研究概览
简要总结
This is a Phase 1, double-blind, placebo-controlled, single ascending dose study in participants with elevated uric acid levels. This study will be conducted in approximately 64 adult male and female participants in the dose escalation phase.
详细描述
Participants will be assigned to 1 of 8 sequential dosing cohorts, each composed of 8 participants (6 active + 2 placebo) who will receive a single dose of PRX-115 or placebo by intravenous (IV) infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females 18 to 65 years of age, inclusive.
- •Serum uric acid greater than 6.0 mg/dL (0.35 mmol/L) at the Screening visit.
- •Body mass index within the range 18.5 to 40 kg/m^2, inclusive, at the Screening visit.
- •Women of childbearing potential may be included only if they have a negative beta human chorionic gonadotropin (β-hCG) test result at Screening.
- •Men and women of childbearing potential and their partners should use double barrier contraception.
排除标准
- •Has any condition known to have arthritis as a clinical manifestation
- •Had greater than or equal to 1 gout flare in the last year prior to either Screening or Day -
- •Has clinical evidence of subcutaneous tophi at either Screening or Day -
- •Estimated glomerular filtration rate (eGFR) value less than or equal to 60 mL/min/1.73m^2
- •History of significant renal disease, and/or presence of renal stones at either Screening or Day -
- •Has a history of anaphylaxis, severe allergic reactions, or severe atopy.
- •History of autoimmune disorders, and/or participant is immunocompromised or treated with immunosuppressive medications.
- •Has evidence of cardiovascular or cerebrovascular disease.
- •History of congestive heart failure, New York Heart Association Class III or IV.
- •BP outside the range of 90 to 150 mm Hg for systolic or 50 to 95 mm Hg for diastolic.
- •Participants with hypertension who are not on stable medication for at least 6 months.
- •Has uncontrolled type 2 diabetes
- •Concurrent treatment with urate lowering drugs (ULDs).
- •Prior exposure to any experimental or marketed uricase (eg, rasburicase [Elitek, Fasturtec], pegloticase [Krystexxa®], pegadricase [SEL-212]).
- •Glucose-6-phosphate dehydrogenase (G6PD) deficiency or known catalase deficiency.
研究组 & 干预措施
PRX-115
Participants will receive a single dose of PRX-115 by IV infusion
干预措施: PRX-115 (Drug)
Placebo
Participants will receive a single dose of placebo by IV infusion
干预措施: Placebo (Drug)
结局指标
主要结局
Number of participants with adverse events receiving PRX-115 compared to placebo
时间窗: Day 0 - Day 85
To assess the safety and tolerability of a single infusion of PRX-115 as assessed by frequency of drug related adverse events, graded by severity.
Number of participants with abnormal clinical vital signs
时间窗: Day 0 - Day 85
Vital signs include pulse rate, blood pressure, respiratory rate and tympanic temperature
Number of participants with abnormal clinically significant results from physical examination
时间窗: Day 0 - Day 85
Number of participants with abnormal clinically significant clinical laboratory results
时间窗: Day 0 - Day 85
Clinical laboratory tests include hematology, coagulation and biochemistry
Number of participants with abnormal clinically significant 12-lead electrocardiogram (ECG) parameters
时间窗: Day 0 - Day 85
次要结局
- PK of PRX-115: Area under the plasma concentration versus time curve (AUC 0-t)(Day 1 - Day 85)
- Immunogenicity of PRX-115: measurement of anti-drug antibody levels(Day 1 - Day 85)
- PK of PRX-115: Time to maximum observed plasma drug concentration (Tmax)(Day 1 - Day 85)
- PK of PRX-115: total body clearance (CL)(Day 1 - Day 85)
- PK of PRX-115: Maximum observed plasma drug concentration (Cmax)(Day 1 - Day 85)
- PK of PRX-115: Terminal elimination half-life (T ½)(Day 1 - Day 85)
- PK of PRX-115: Area under the plasma concentration versus time curve (AUC 0-inf)(Day 1 - Day 85)
- Pharmacodynamics of PRX-115: blood uric acid levels(Day 0 - Day 85)
- PK of PRX-115: volume of distribution during the terminal phase (Vd)(Day 1 - Day 85)