A Randomized, Double-blind, Placebo-Controlled, Phase 3 Study of Olezarsen (ISIS 678354) in Patients With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease (Established or at Increased Risk for), or With Severe Hypertriglyceridemia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,478
- 试验地点
- 168
- 主要终点
- Percent Change From Baseline to Week 25 in Fasting Triglycerides (TG) Compared to Placebo
研究概览
简要总结
The purpose of the study is to evaluate the effect of olezarsen on percent change in fasting triglyceride (TG) levels compared to placebo in participants with hypertriglyceridemia and atherosclerotic cardiovascular disease, or with severe hypertriglyceridemia.
详细描述
This is a Phase 3, multi-center, placebo-controlled study in approximately 1475 participants with hypertriglyceridemia and atherosclerotic cardiovascular disease. The study consists of 3 periods: 1) Screening Period: Week -12 to Week -1 (up to 12 weeks); 2) Treatment Period up to Week 53; and 3) Post-Treatment Follow-up Period: Week 54 to Week 66 (13 weeks). Participants enrolled will receive olezarsen or placebo once every 4 weeks during the 53-week Treatment Period.
The Screening Period was extended with no impact to overall study timelines.
A coronary computed tomographic angiography (CTA) sub study will be performed to assess whether triglyceride lowering through inhibition of apoC-III protein synthesis may reduce coronary plaque progression.
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
- •Participants must fall into 1 of the following groups (a or b):
- •a. Hypertriglyceridemia with fasting TG ≥200 mg/dL (2.26 millimoles per liter [mmol/L]) and <500 mg/dL (5.65 mmol/L) with either
- •Clinical diagnosis of atherosclerotic cardiovascular disease (ASCVD) or
- •At increased risk for ASCVD
- •b. Severe hypertriglyceridemia with fasting TG ≥500 mg/dL (5.65 mmol/L)
- •Participants should be on standard of care (SOC) lipid-lowering medications per local guidelines. Lipid-lowering medications should be optimized and stabilized for at least 4 weeks prior to Screening to minimize changes in these medications during the study.
排除标准
- •Hemoglobin A1c (HbA1c) ≥ 9.5% at Screening
- •Alanine aminotransferase or aspartate aminotransferase > 3.0 × upper limit of normal
- •Total bilirubin > 1.5 upper limit of normal unless due to Gilbert's syndrome
- •Estimated GFR < 30 mL/min/1.73 m^2
- •NOTE: Other Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Olezarsen
Participants will be randomized to receive multiple doses of olezarsen, once every 4 weeks by subcutaneous (SC) injection up to Week 49.
干预措施: Olezarsen (Drug)
Placebo
Participants will be randomized to receive olezarsen-matching placebo, once every 4 weeks by SC injection up to Week 49.
干预措施: Placebo (Drug)
结局指标
主要结局
Percent Change From Baseline to Week 25 in Fasting Triglycerides (TG) Compared to Placebo
时间窗: Baseline to Week 25
次要结局
- Percent Change From Baseline to Weeks 25 and 53 in Fasting Apolipoprotein B (apoB) Compared to Placebo(Baseline to Weeks 25 and 53)
- Percent Change From Baseline to Weeks 25 and 53 in Fasting Very Low-Density Lipoprotein-Cholesterol (VLDL)-C Compared to Placebo(Baseline to Weeks 25 and 53)
- Percent Change From Baseline to Week 53 in Fasting TG Compared to Placebo(Baseline to Week 53)
- Percent Change From Baseline to Weeks 25 and 53 in Fasting Apolipoprotein C-III (apoC-III) Compared to Placebo(Baseline to Weeks 25 and 53)
- Proportion of Participants who Achieve Fasting TG <150 Milligrams per Deciliter (mg/dL) at Weeks 25 and 53 Compared to Placebo(Baseline, Weeks 25 and 53)
- Percent Change From Baseline to Weeks 25 and 53 in Fasting non-High Density Lipoprotein-Cholesterol (HDL)-C Compared to Placebo(Baseline to Weeks 25 and 53)
- Percent Change From Baseline to Weeks 25 and 53 in Fasting High-Density Lipoprotein-Cholesterol (HDL)-C Compared to Placebo(Baseline to Weeks 25 and 53)
- Percent Change From Baseline to Weeks 25 and 53 in Fasting Remnant Cholesterol Compared to Placebo(Baseline to Weeks 25 and 53)
- Percent Change From Baseline to Weeks 25 and 53 in Fasting Low-Density Lipoprotein-Cholesterol (LDL)-C Compared to Placebo(Baseline to Weeks 25 and 53)