A Phase I Single Ascending Dose Safety, Pharmacokinetic and Pharmacodynamics Study of SEL-212 in Subjects With Elevated Blood Uric Acid
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 63
- 试验地点
- 6
- 主要终点
- Safety and tolerability as assessed by frequency of drug related adverse events, graded by severity
研究概览
简要总结
This Study will first evaluate the safety and pharmacokinetics of a single intravenous dose of SEL-110, a nanoparticle containing rapamycin, in subjects with elevated blood uric acid levels. This will be followed, in separate subjects, by evaluation of the safety, pharmacokinetics, pharmacodynamics and immunogenicity of a single intravenous dose of SEL-212, SEL-037 (pegsiticase) plus SEL-110, in subjects with elevated blood uric acid levels. Uricase is an enzyme that converts uric acid to the readily soluble allantoin that is then excreted and SEL-110 is designed to prevent unwanted anti-drug-antibodies (ADAs) from forming.
详细描述
This Study will first evaluate the safety and pharmacokinetics of a single intravenous dose of SEL-110, a nanoparticle containing rapamycin, in subjects with elevated blood uric acid levels. This will be followed, in separate subjects, by evaluation of the safety, pharmacokinetics, pharmacodynamics and immunogenicity of a single intravenous dose of SEL-212, SEL-037 (pegsiticase) plus SEL-110, in subjects with elevated blood uric acid levels. Uricase is an enzyme that converts uric acid to the readily soluble allantoin that is then excreted and SEL-110 is designed to prevent unwanted anti-drug-antibodies (ADAs) from forming. Cohorts of subjects in the SEL-110 only arms of the study will be given a single, ascending intravenous dose of SEL-110 and then monitored for safety and rapamycin levels (pharmacokinetics) over 30 days. Cohorts of subjects in the SEL-212 arms of the study will be given a single, ascending intravenous dose of SEL-110 with a fixed dose of SEL-037 and then monitored for safety, rapamycin levels, SEL-037 levels, uric acid levels and anti-drug-antibodies (ADAs) to SEL-037 for 30 days. One additional control group with receive a single intravenous infusion of SEL-037 at a fixed dose and then monitored for safety, SEL-037 levels, uric acid levels and anti-drug-antibodies (ADAs) to SEL-037 for 30 days
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
- None
入排标准
- 年龄范围
- 21 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects ages 21 to 70 inclusive. Female subjects must be of non-childbearing potential;
- •Has at the screening visit a serum uric acid ≥ 6 mg/dL, with or without a history of gout;
- •The use of allopurinol, febuxostat (Uloric®), or probenecid as uric acid-lowering therapy is permissible if dosing has been stable for at least the month prior to the screening visit;
- •Has adequate venous access and able to receive IV therapy;
- •Evidence of a personally signed and dated informed consent document indicating that subject has been informed of all pertinent aspects of the study;
排除标准
- •Prior exposure to any experimental or marketed uricase (for arms receiving SEL-037 or SEL-212);
- •History of any allergy to pegylated products;
- •Glucose-6-phosphate dehydrogenase deficiency or known catalase deficiency;
- •History of hematological or autoimmune disorders, is immunosuppressed or immunocompromised;
- •Presently taking a drug classified as CYP3A4 inducer or inhibitor;
- •Has participated in a clinical trial within 30 days of the Screening;
研究组 & 干预措施
SEL-037
Single intravenous dose of SEL-037 (pegsiticase)
干预措施: SEL-037 (Biological)
SEL-110
Single intravenous dose of SEL-110
干预措施: SEL-110 (Drug)
SEL-110
Single intravenous dose of SEL-110
干预措施: SEL-212 (Biological)
SEL-212
Single intravenous dose of SEL-110 plus SEL-037 (pegsiticase)
干预措施: SEL-212 (Biological)
结局指标
主要结局
Safety and tolerability as assessed by frequency of drug related adverse events, graded by severity
时间窗: 30 days
To assess the safety and tolerability of a single infusion of SEL-110, SEL-212 or SEL-037 as assessed by frequency of drug related adverse events, graded by severity
次要结局
- Immunogenicity of SEL-037 (measurement of anti-drug antibody levels)(30 days)
- Pharmacokinetics of SEL-110 (AUC)(30 days)
- Pharmacokinetics of SEL-037 (AUC)(30 days)
- Pharmacodynamics of SEL-037 (blood uric acid levels)(30 days)