A Placebo-Controlled, Dose-Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of ISIS 703802, Targeting ANGPTL3, Administered Subcutaneously to Healthy Volunteers With Elevated Triglycerides and Subjects With Familial Hypercholesterolemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Safety and tolerability of single and multiple doses of IONIS ANGPTL3-LRx (incidence, severity, and dose-relationship of adverse effects and changes in the laboratory parameters)
研究概览
简要总结
The purpose is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS ANGPTL3-LRx (ISIS 703802) given to healthy volunteer subjects with elevated triglycerides and subjects with familial hypercholesterolemia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 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
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cohorts A, D: Placebo
Participants received a single-dose of IONIS ANGPTL3-LRx-matching placebo subcutaneously on Day 1.
干预措施: Placebo (Drug)
Cohorts A, D: IONIS ANGPTL3-LRx 20 mg
Participants received a single-dose of IONIS ANGPTL3-LRx 20 milligrams (mg) subcutaneously on Day 1.
干预措施: IONIS ANGPTL3-LRx (Drug)
Cohorts A, D: IONIS ANGPTL3-LRx 120 mg
Participants received a single-dose of IONIS ANGPTL3-LRx 120 mg subcutaneously on Day 1.
干预措施: IONIS ANGPTL3-LRx (Drug)
Cohorts B, C: Placebo
Participants received a single-dose of IONIS ANGPTL3-LRx-matching placebo subcutaneously on Day 1.
干预措施: Placebo (Drug)
Cohorts B, C: IONIS ANGPTL3-LRx 40 mg
Participants received a single-dose of IONIS ANGPTL3-LRx 40 mg subcutaneously on Day 1.
干预措施: IONIS ANGPTL3-LRx (Drug)
Cohorts B, C: IONIS ANGPTL3-LRx 80 mg
Participants received a single-dose of IONIS ANGPTL3-LRx 80 mg subcutaneously on Day 1.
干预措施: IONIS ANGPTL3-LRx (Drug)
Cohorts AA-DD: Placebo
Participants received IONIS ANGPTL3-LRx-matching placebo subcutaneously once per week for 6 weeks.
干预措施: Placebo (Drug)
Cohorts AA-DD: IONIS ANGPTL3-LRx 10 mg
Participants received IONIS ANGPTL3-LRx 10 mg subcutaneously once per week for 6 weeks.
干预措施: IONIS ANGPTL3-LRx (Drug)
Cohorts AA-DD: IONIS ANGPTL3-LRx 20 mg
Participants received IONIS ANGPTL3-LRx 20 mg subcutaneously once per week for 6 weeks.
干预措施: IONIS ANGPTL3-LRx (Drug)
Cohorts AA-DD: IONIS ANGPTL3-LRx 40 mg
Participants received IONIS ANGPTL3-LRx 40 mg subcutaneously once per week for 6 weeks.
干预措施: IONIS ANGPTL3-LRx (Drug)
Cohorts AA-DD: IONIS ANGPTL3-LRx 60 mg
Participants received IONIS ANGPTL3-LRx 60 mg subcutaneously once per week for 6 weeks.
干预措施: IONIS ANGPTL3-LRx (Drug)
结局指标
主要结局
Safety and tolerability of single and multiple doses of IONIS ANGPTL3-LRx (incidence, severity, and dose-relationship of adverse effects and changes in the laboratory parameters)
时间窗: Up to Day 127
The safety and tolerability of IONIS ANGPTL3-LRx will be assessed by determining the incidence, severity, and dose-relationship of adverse effects and changes in the laboratory parameters by dose. Safety results in subjects dosed with IONIS ANGPTL3-LRx will be compared with those from subjects dosed with placebo.
Pharmacokinetics after single and multiple doses of IONIS ANGPTL3-LRx.
时间窗: Up to Day 127
The plasma pharmacokinetics (concentration-time results) of IONIS ANGPTL3-LRx (unconjugated and conjugated ASO) will be assessed following single and multiple-dose SC administration. The amount of IONIS ANGPTL3-LRx excreted in urine at selected 24-hour intervals will also be determined.
Pharmacodynamics of IONIS ANGPTL3-LRx (Changes in serum ANGPTL3 levels)
时间窗: Up to Day 127
Changes in serum angiopoietin-like 3 (ANGPTL3) levels compared to baseline.
次要结局
- Pharmacodynamic effects of IONIS ANGPTL3-LRx(Up to Day 127)