NCT06347016进行中（未招募）3 期
Double-blind, Placebo-controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Plozsiran in Adults With Severe Hypertriglyceridemia
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 311
- 试验地点
- 297
- 主要终点
- Percent change in fasting serum TG levels from baseline to Month 12 compared to placebo
研究概览
简要总结
This Phase 3 study will evaluate the safety and efficacy of plozasiran injection (ARO-APOC3) in adult participants with severe hypertriglyceridemia (SHTG). After providing informed consent eligible participants will be randomized to receive 4 doses (once every 3 months) of plozasiran or placebo, and be evaluated for efficacy and safety. After Month 12, eligible participants will be offered an opportunity to continue in an optional open-label extension under a separate protocol.
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
- •Established diagnosis of severe hypertriglyceridemia (SHTG) and prior documented evidence (medical history) of fasting TG levels of ≥500 mg/dL (≥5.65 mmol/L)
- •Mean fasting TG level ≥500 mg/dL (≥5.65 mmol/L) collected at 2 separate and consecutive visits at least 7 days apart and no more than 17 days apart during the screening period
- •Fasting low density lipoprotein-cholesterol (LDL-C) ≤130 mg/dL (≤3.37 mmol/L) at screening
- •Screening HbA1C ≤9.0%
- •Must be on standard of care lipid-lowering medications per local guidelines (unless documented as intolerant as determined by the Investigator, including an inability to safely administer or re-administer a specific drug because of fear, preference, genetic, clinical, or metabolic considerations, or due to a previous adverse reaction associated with, attributed to, or caused by specific drug)
排除标准
- •Use of any hepatocyte-targeted small interfering ribonucleic acid (siRNA) that targets lipids and/or triglycerides within 365 days before Day 1 (except inclisiran, which is permitted). Administration of investigational drug and inclisiran must be separated by at least 4 weeks
- •Use of any other hepatocyte-targeted siRNA or antisense oligonucleotide molecule within 60 days or within 5-half-lives before Day 1 based on plasma pharmacokinetics (PK), whichever is longer (except inclisiran, which is permitted)
- •Known diagnosis of familial chylomicronemia syndrome (FCS) (type 1 Hyperlipoproteinemia) by documentation of confirmed homozygote or double heterozygote for loss-of-function mutations in type 1- causing genes
- •Body mass index >45kg/m^2
- •Note: Additional Inclusion/Exclusion criteria may apply per protocol
研究组 & 干预措施
Placebo
Placebo Comparator
calculated volume to match active treatment by sc injection
干预措施: Placebo (Drug)
Plozasiran Injection
Experimental
4 doses of plozasiran (ARO-APOC3) by subcutaneous (sc) injection
干预措施: Plozasiran Injection (Drug)
结局指标
主要结局
Percent change in fasting serum TG levels from baseline to Month 12 compared to placebo
时间窗: Baseline, Month 12
次要结局
- Change from Baseline in Fasting Blood Glucose During the Treatment Period Compared to Placebo(From first dose of study drug through Month 12)
- Change from Baseline in C-Peptide During the Treatment Period Compared to Placebo(From first dose of study drug through Month 12)
- Change from Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) During the Treatment Period Compared to Placebo(From first dose of study drug through Month 12)
- Change from Baseline in Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) Associated with Worsening Glycemic Control During the Treatment Period Compared to Placebo(From first dose of study drug through Month 12)
- Initiation of New Medication for Hyperglycemia among Study Participants Not Known to Have Pre-existing Diabetes Mellitus During the Treatment Period Compared to Placebo(From first dose of study drug through Month 12)
- Adjudicated Major Adverse Cardiovascular Events (MACE) Rates During the Treatment Period Compared to Placebo(From first dose of study drug through Month 12)
- Incidence of Anti-drug Antibodies (ADA) to Plozasiran in Subjects Receiving Plozasiran Over Time Through Month 12(From first dose of study drug through Month 12)
- Titers of Anti-drug Antibodies (ADA) to Plozasiran in Subjects Receiving Plozasiran Over Time Through Month 12(From first dose of study drug through Month 12)
- Percent Change in Fasting Serum TG Levels from Baseline to Month 10 Compared to Placebo(Baseline, Month 10)
- Proportion of subjects who achieve fasting TG levels of <500 mg/dL (<5.65 mmol/L) at Month 12 compared to placebo(Baseline, Month 12)
- Proportion of Subjects Who Achieve Fasting TG Levels of < 150 mg/dL (<1.69 mmol/L) at Month 12 compared to placebo(Baseline, Month 12)
- Percent change in remnant cholesterol (VLDL-C) from baseline to Month 12 compared to placebo(Baseline, Month 12)
- Percent change in non-HDL-C from baseline to Month 12 compared to placebo(Baseline, Month 12)
- Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs) Over Time through Month 12 as Compared to Placebo(From first dose of study drug through Month 12)
- Incidence Rates of New-Onset Diabetes Mellitus (NODM) Throughout the Course of Treatment(From first dose of study drug through Month 12)
- Incidence Rates of Impaired Glucose Tolerance Throughout the Course of Treatment(From first dose of study drug through Month 12)
- Incidence Rates of Worsening of Existing Diabetes Throughout the Course of Treatment(From first dose of study drug through Month 12)
- Change from Baseline in Hemoglobin A1c (HbA1c) and Other Glycemic Control Parameters During the Treatment Period Compared to Placebo(From first dose of study drug through Month 12)
- Percent Change in Fasting Serum TG Levels from Baseline to Month 10 Compared to Placebo(Baseline, Month 10)
- Proportion of subjects who achieve fasting TG levels of <500 mg/dL (<5.65 mmol/L) at Month 12 compared to placebo(Baseline, Month 12)
- Proportion of Subjects Who Achieve Fasting TG Levels of < 150 mg/dL (<1.69 mmol/L) at Month 12 compared to placebo(Baseline, Month 12)
- Percent change in remnant cholesterol (VLDL-C) from baseline to Month 12 compared to placebo(Baseline, Month 12)
- Percent change in non-HDL-C from baseline to Month 12 compared to placebo(Baseline, Month 12)
- Adjudicated AP Event Rate During the Treatment Period Compared to Placebo From Day 1 to Month 12(Month 12)
- Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs) Over Time through Month 12 as Compared to Placebo(From first dose of study drug through Month 12)
- Incidence Rates of New-Onset Diabetes Mellitus (NODM) Throughout the Course of Treatment(From first dose of study drug through Month 12)
- Incidence Rates of Impaired Glucose Tolerance Throughout the Course of Treatment(From first dose of study drug through Month 12)
- Incidence Rates of Worsening of Existing Diabetes Throughout the Course of Treatment(From first dose of study drug through Month 12)
- Change from Baseline in Hemoglobin A1c (HbA1c) and Other Glycemic Control Parameters During the Treatment Period Compared to Placebo(From first dose of study drug through Month 12)
- Change from Baseline in Fasting Blood Glucose During the Treatment Period Compared to Placebo(From first dose of study drug through Month 12)
- Change from Baseline in C-Peptide During the Treatment Period Compared to Placebo(From first dose of study drug through Month 12)
- Change from Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) During the Treatment Period Compared to Placebo(From first dose of study drug through Month 12)
- Change from Baseline in Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) Associated with Worsening Glycemic Control During the Treatment Period Compared to Placebo(From first dose of study drug through Month 12)
- Initiation of New Medication for Hyperglycemia among Study Participants Not Known to Have Pre-existing Diabetes Mellitus During the Treatment Period Compared to Placebo(From first dose of study drug through Month 12)
- Adjudicated Major Adverse Cardiovascular Events (MACE) Rates During the Treatment Period Compared to Placebo(From first dose of study drug through Month 12)
- Incidence of Anti-drug Antibodies (ADA) to Plozasiran in Subjects Receiving Plozasiran Over Time Through Month 12(From first dose of study drug through Month 12)
- Titers of Anti-drug Antibodies (ADA) to Plozasiran in Subjects Receiving Plozasiran Over Time Through Month 12(From first dose of study drug through Month 12)
研究者
研究点 (297)
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