A Randomized, Double-blind, Placebo-Controlled, Phase 2b Study of ISIS 678354 in Patients With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease (Established or at Increased Risk for), and/or With Severe Hypertriglyceridemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 154
- 试验地点
- 24
- 主要终点
- Percent Change From Baseline at Month 6 (average of Weeks 25 and 27) in Fasting Triglycerides (TG)
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 at Months 6 and 12 and the percentage of participants who achieve different thresholds in fasting TG. Another objective is to evaluate the effect of olezarsen on percent change in fasting apolipoprotein C-III (apoC-III), very low-density lipoprotein cholesterol (VLDL-C), remnant cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), HDL-C, total cholesterol (TC), apolipoprotein B (apoB), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein A-1 (apoA-1).
详细描述
This will be a multi-center, randomized, double-blind, placebo-controlled study in approximately 152 participants with hypertriglyceridemia (triglycerides > 150 milligrams per deciliter [mg/dL]) and established or at increased risk for atherosclerotic cardiovascular disease, and/or with severe hypertriglyceridemia. The study will have an up to 8-week screening period, a 53-week treatment period, and a 13-week post-treatment follow-up period.
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
- •Aged ≥ 18 years at the time of informed consent
- •Fall into at least 1 of the following groups (a or b):
- •Hypertriglyceridemia with fasting TG ≥ 150 mg/dL (1.69 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
- •Severe hypertriglyceridemia with fasting TG ≥ 500 mg/dL (5.65 mmol/L).
- •Participants must be on standard-of-care (SOC), lipid-lowering medications per local guidelines.
- •Participants must be willing to comply with diet and lifestyle recommendations as able.
排除标准
- •Diabetes with any of the following:
- •Newly diagnosed within 12 weeks of screening
- •Hemoglobin A1C (HbA1c) ≥ 9.5% at Screening
- •Change in basal insulin regimen > 20% within 3 months prior to Screening
- •For participants with type 1 diabetes: episode of diabetic ketoacidosis, or ≥ 3 episodes of severe hypoglycemia within 6 months prior to Screening
- •Acute coronary syndrome or stroke/transient ischemic attack (TIA) within 6 months prior to Screening
- •Major surgery, peripheral revascularization, or non-urgent percutaneous coronary intervention (PCI) within 3 months prior to Screening, or upcoming planned major surgery or major procedure (e.g., arterial revascularization) during the course of the study
- •Active pancreatitis within 4 weeks prior to Screening
研究组 & 干预措施
Olezarsen
Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection for up to 49 weeks.
干预措施: Olezarsen (Drug)
Placebo
Olezarsen-matching placebo will be administered once every 4 weeks by SC injection for up to 49 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Percent Change From Baseline at Month 6 (average of Weeks 25 and 27) in Fasting Triglycerides (TG)
时间窗: Baseline and Month 6
次要结局
- Proportion of Participants with Baseline TG < 500 mg/dL (5.65 mmol/L) Who Achieve Fasting TG < 150 mg/dL (1.69 mmol/L) at Month 12(Baseline and Month 12)
- Proportion of Participants with Baseline TG ≥ 500 mg/dL Who Achieve Fasting TG < 500 mg/dL at Month 12(Baseline and Month 12)
- Percent Change From Baseline at Months 6 and 12 in Fasting Non-HDL-C(Baseline, Months 6 and 12)
- Adjudicated acute pancreatitis event rate during the Treatment Period compared to placebo in patients with ≥ 2 events of adjudicated acute pancreatitis in 5 years prior to enrollment.(Baseline through Month 12)
- Proportion of Participants with Baseline TG < 500 mg/dL (5.65 mmol/L) Who Achieve Fasting TG < 150 milligrams per deciliter (mg/dL) (1.69 millimoles per liter [mmol/L]) at Month 6(Baseline and Month 6)
- Percent Change From Baseline at Months 6 and 12 in Fasting LDL-C(Baseline, Months 6 and 12)
- Percent Change From Baseline at Months 6 and 12 in Fasting Remnant Cholesterol(Baseline, Months 6 and 12)
- Percent Change From Baseline at Months 6 and 12 in Fasting HDL-C(Baseline, Months 6 and 12)
- Percent Change From Baseline at Months 6 and 12 in Fasting TC(Baseline, Months 6 and 12)
- Percent Change From Baseline at Months 6 and 12 in apoA-1(Baseline, Months 6 and 12)
- Adjudicated acute pancreatitis event rate during the Treatment Period compared to placebo.(Baseline through Month 12)
- Percent Change From Baseline at Month 12 in Fasting TG(Baseline and Month 12)
- Proportion of Participants with Baseline TG ≥ 500 mg/dL Who Achieve Fasting TG < 500 mg/dL (5.65 mmol/L) at Month 6(Baseline and Month 6)
- Percent Change From Baseline at Months 6 and 12 in Fasting VLDL-C(Baseline, Months 6 and 12)
- Percent Change From Baseline at Months 6 and 12 in Fasting apoB(Baseline, Months 6 and 12)
- Percent Change From Baseline at Months 6 and 12 in Fasting apoC-III(Baseline, Months 6 and 12)