NCT06347003进行中（未招募）3 期
Double-blind, Placebo-controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Plozasiran in Adults With Severe Hypertriglyceridemia
适应症
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 446
- 试验地点
- 243
- 主要终点
- Percent Change in Fasting Serum Triglyceride (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
- •Males, or nonpregnant (who do not plan to become pregnant) nonlactating females, who are ≥18 years of age at screening
- •Established diagnosis of severe hypertriglyceridemia (SHTG) and prior documented evidence (medical history) of fasting TG levels of ≥ 500 mg/dL (≥5.65mmol/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%
- •Willing to follow diet counseling and maintain a stable low-fat diet
- •Must be on standard of care lipid and TG 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
- •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
- •Acute pancreatitis within 4 weeks prior to screening
- •Body mass index >45kg/m^2
- •Note: Additional Inclusion/Exclusion criteria may apply per protocol
结局指标
主要结局
Percent Change in Fasting Serum Triglyceride (TG) Levels from Baseline to Month 12 Compared to Placebo
时间窗: Baseline, Month 12
Percent change in fasting serum TG levels from baseline to Month 12 (V10 and V11) compared to placebo
Percent change in fasting serum TG levels from baseline to Month 12 (V10 and V11) compared to placebo
次要结局
- 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 Participants 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 Participants Receiving Plozasiran Over Time Through Month 12(From first dose of study drug through Month 12)
- Change and/or percent change from baseline to Month 12 in liver fat content using MRI-PDFF, only in a subset of subjects(Baseline, Month 12)
- Change from baseline in HbA1c 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)
- Percent Change in Fasting Serum TG Levels from Baseline to Month 10 Compared to Placebo(Baseline, Month 10)
- Proportion of Participants Who Achieve Fasting TG Levels of <500 mg/dL (<5.65 mmol/L) at Month 12 Compared to Placebo(Baseline, Month 12)
- Proportion of Participants 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 participants 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)
- Percent Change in Fasting Serum TG Levels from Baseline to Month 10 Compared to Placebo(Baseline, Month 10)
- Proportion of Participants Who Achieve Fasting TG Levels of <500 mg/dL (<5.65 mmol/L) at Month 12 Compared to Placebo(Baseline, Month 12)
- Proportion of Participants 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 participants 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 HbA1c 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 Participants 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 Participants Receiving Plozasiran Over Time Through Month 12(From first dose of study drug through Month 12)
- Change and/or percent change from baseline to Month 12 in liver fat content using MRI-PDFF, only in a subset of subjects(Baseline, Month 12)
研究者
Jennifer Hellawell
Scientific
Arrowhead Pharmaceuticals Inc.
研究点 (243)
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