A Double-Blind, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of Plozasiran in Adults With Mixed Dyslipidemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 353
- 试验地点
- 30
- 主要终点
- Percent Change From Baseline at Week 24 in Fasting TG
研究概览
简要总结
Participants who have met all protocol eligibility criteria will be randomly assigned to treatment (ARO-APOC3 or placebo) in a double-blind fashion and will be evaluated for safety and efficacy over 48 weeks. Participants will be counseled to remain on a specified diet throughout the study, as recommended by the Investigator in accordance with local standards of care. After week 48, participants will be eligible and invited to consent and continue in an open-label extension study. All placebo participants who opt to continue will switch to active drug (ARO-APOC3) during the extension study.
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
- •Based on medical history, prior evidence of triglycerides (TG) ≥ 150 milligrams (mg)/deciliter (dL) and ≤ 499 mg/dL
- •Fasting levels at Screening of non-high-density lipoprotein cholesterol (non-HDL-C) ≥ 100 mg/dL or low-density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dL after at least 2 weeks of stable diet and 4 weeks on stable optimal statin therapy
- •Mean fasting TG ≥ 150 mg/dL and ≤ 499 mg/dL during Screening collected at two separate and consecutive visits and at least 7 days apart and not more than 17 days apart
- •Willing to follow diet counseling as per Investigator judgment based on local standard of care
- •Participants of childbearing potential (males & females) must use highly effective contraception during the study and for at least 24 weeks following the last dose of study medication. Males must not donate sperm and females must not donate eggs during the study and for at least 24 weeks following the last dose of study medication.
- •Women of childbearing potential must have a negative pregnancy test at Screening and cannot be breastfeeding
- •Women of childbearing potential on hormonal contraceptives must be stable on the medication for ≥ 2 menstrual cycles prior to Day 1
- •Willing to provide written informed consent and to comply with study requirements
排除标准
- •Current use or use within 365 days from Day 1 of any hepatocyte targeted short interfering RNA oligonucleotides (siRNA) or antisense oligonucleotide molecule
- •Active pancreatitis within 12 weeks prior to Day 1
- •Any planned bariatric surgery or similar procedures to induce weight loss from consent through end of study
- •Acute coronary syndrome event within 24 weeks of Day 1
- •History of major surgery within 12 weeks of Day 1 or planned major surgery during the study
- •Planned coronary intervention (such as, stent placement or heart bypass) during the study
- •New York Heart Association (NYHA) Class II, III or IV heart failure or last known ejection fraction of <30%
- •Uncontrolled hypertension
- •Known history of human immunodeficiency virus (HIV) infection, seropositive for Hepatitis B virus (HBV), seropositive for Hepatitis C virus (HCV)
- •Uncontrolled hypothyroidism or hyperthyroidism
- •Hemorrhagic stroke within 24 weeks of Day 1
- •History of bleeding diathesis or coagulopathy
- •Current diagnosis of nephrotic syndrome
- •Systemic use of corticosteroids or anabolic steroids within 4 weeks prior to Day 1 or planned use during the study
- •Malignancy within the last 2 years prior to date of consent requiring systemic treatment (some exceptions apply)
- •Note: Additional inclusion/exclusion criteria may apply per protocol
研究组 & 干预措施
Placebo
Volume-matched placebo SC injection on Day 1 and Week 12 for a total of 2 injections
干预措施: Placebo (Drug)
ARO-APOC3 50 mg Q24W
ARO-APOC3 50 mg SC injection on Day 1 and Week 24 (Q24W) for a total of 2 injections
干预措施: ARO-APOC3 (Drug)
ARO-APOC3 50 mg Q12W
ARO-APOC3 50 mg SC injection on Day 1 and Week 12 (Q12W) for a total of 2 injections
干预措施: ARO-APOC3 (Drug)
ARO-APOC3 10 mg Q12W
ARO-APOC3 10 milligrams (mg) subcutaneous (SC) injection on Day 1 and Week 12 (Q12W) for a total of 2 injections
干预措施: ARO-APOC3 (Drug)
ARO-APOC3 25 mg Q12W
ARO-APOC3 25 mg SC injection on Day 1 and Week 12 (Q12W) for a total of 2 injections
干预措施: ARO-APOC3 (Drug)
结局指标
主要结局
Percent Change From Baseline at Week 24 in Fasting TG
时间窗: Baseline, Week 24
Least square (LS) mean and standard error (SE) were calculated using mixed model repeated measures (MMRM) which included treatment arm, study visit, and baseline value as model terms and treatment by visit and treatment by baseline as interaction terms.
次要结局
- Percent Change From Baseline Over Time Through Week 48 in Fasting TG(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET))
- Percent Change From Baseline at Week 24 in Apolipoprotein (Apo)C-III(Baseline, Week 24)
- Percent Change From Baseline Over Time Through Week 48 in ApoC-III(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/ET)
- Percent Change From Baseline at Week 24 in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C)(Baseline, Week 24)
- Percent Change From Baseline Over Time Through Week 48 in Fasting Non-HDL-C(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/ET)
- Percent Change From Baseline at Week 24 in Fasting High-Density Lipoprotein Cholesterol (HDL-C)(Baseline, Week 24)
- Percent Change From Baseline Over Time Through Week 48 in Fasting HDL-C(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/ET)
- Percent Change From Baseline at Week 24 in Fasting Total Apolipoprotein B (ApoB)(Baseline, Week 24)
- Percent Change From Baseline Over Time Through Week 48 in Fasting Total ApoB(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/ET)
- Percent Change From Baseline at Week 24 in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C)(Baseline, Week 24)
- Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/ET)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(Up to Week 48)