NCT05089084已完成3 期
A Phase 3 Study to Evaluate the Efficacy and Safety of ARO-APOC3 in Adults With Familial Chylomicronemia Syndrome
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 58
- 主要终点
- Percent Change From Baseline at Month 10 in Fasting Triglycerides (TG)
研究概览
简要总结
The purpose of AROAPOC3-3001 is to evaluate the efficacy and safety of ARO-APOC3 (plozasiran) in adult participants with familial chylomicronemia syndrome (FCS). Participants who have met all eligibility criteria will be randomized to receive 4 doses of plozasiran or matching placebo administered subcutaneously. Participants who complete the randomized period will continue in a 2-year open-label extension period where all participants will receive plozasiran.
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
- •Fasting triglycerides (TG) ≥ 10 mmol/L (≥ 880 mg/dL) at screening refractory to standard lipid lowering therapy
- •Diagnosis of FCS
- •Willing to follow dietary counseling as per investigator judgement 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 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
排除标准
- •Current use or use within the last 365 Days from Day 1 of any hepatocyte-targeted siRNA or antisense oligonucleotide molecule
- •Diabetes mellitus newly diagnosed within 12 weeks of Screening or where HbA1c ≥ 9.0% at Screening
- •Active pancreatitis within 12 weeks before Day 1
- •History of acute coronary syndrome event within 24 weeks of Day 1
- •History of major surgery within 12 weeks of Day 1
- •Uncontrolled hypertension
- •On treatment with human immunodeficiency virus (HIV) antiretroviral therapy
- •Seropositive for hepatitis B virus (HBV) or hepatitis C virus (HCV)
- •New York Heart Association (NYHA) Clas II, III, or IV heart failure
- •Note: Additional Inclusion/Exclusion criteria may apply per protocol
研究组 & 干预措施
Placebo for ARO-APOC3 (Plozasiran) 25 mg
Placebo Comparator
Randomized Period: volume-matched placebo every 3 months (Q3M) for a total of 4 doses.
Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.
干预措施: Placebo (Drug)
Placebo for ARO-APOC3 (Plozasiran) 50 mg
Placebo Comparator
Randomized Period: volume-matched placebo every 3 months (Q3M) for a total of 4 doses.
Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.
干预措施: Placebo (Drug)
ARO-APOC3 (Plozasiran) 25 mg
Experimental
Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses.
Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.
干预措施: Plozasiran (Drug)
Placebo for ARO-APOC3 (Plozasiran) 25 mg
Placebo Comparator
Randomized Period: volume-matched placebo every 3 months (Q3M) for a total of 4 doses.
Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.
干预措施: Plozasiran (Drug)
ARO-APOC3 (Plozasiran) 50 mg
Experimental
Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses.
Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.
干预措施: Plozasiran (Drug)
Placebo for ARO-APOC3 (Plozasiran) 50 mg
Placebo Comparator
Randomized Period: volume-matched placebo every 3 months (Q3M) for a total of 4 doses.
Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.
干预措施: Plozasiran (Drug)
结局指标
主要结局
Percent Change From Baseline at Month 10 in Fasting Triglycerides (TG)
时间窗: Baseline, Month 10
次要结局
- Percent Change From Baseline in Fasting TG at Month 10 and Month 12 (Averaged)(Baseline, Month 10, Month 12)
- Percent Change From Baseline in Apolipoprotein C-III (APOC3) at Month 10(Baseline, Month 10)
- Percent Change From Baseline in Fasting APOC3 at Month 12(Baseline, Month 12)
- Percentage of Participants With Positively Adjudicated Events of Acute Pancreatitis (Randomized Period)(From first dose of study drug through Month 12 (Randomized Period))
- Percentage of Participants With Positively Adjudicated Events of Acute Pancreatitis (Open-Label Period)(From first dose of study drug through Month 36 (Open-Label Period))
- Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Month 10(Baseline, Month 10)
- Percent Change From Baseline in Non-HDL-C at Month 12(Baseline, Month 12)
- Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Month 10(Baseline, Month 10)
- Percent Change From Baseline in HDL-C at Month 12(Baseline, Month 12)
- Percent Change From Baseline in Fasting Triglycerides (TG) at Month 12(Baseline, Month 12)
- Percentage of Participants Achieving Fasting TG of <500, 880, and 1000 mg/dL at Month 10(Month 10)
- Percentage of Participants Achieving Fasting TG of <500, 880, and 1000 mg/dL at Month 12(Month 12)
- Percentage of Participants Achieving ≥40% and ≥70% Reduction From Baseline in Fasting TG at Month 10(Baseline, Month 10)
- Change From Baseline in Fasting TG Over Time(Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
- Percent Change From Baseline in Fasting TG Over Time(Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
- Number of Participants With Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs; Randomized Period)(From first dose of study drug through Month 12 (Randomized Period))
- Number of Participants With Treatment-Emergent AEs and/or SAEs (Open-Label Period)(From first dose of open-label study drug through Month 36 (Open-Label Period))
研究者
研究点 (58)
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Sanofi Secures Chinese Approval for Two Breakthrough Therapies Targeting Rare Cardiovascular and Metabolic Disorders- China's National Medical Products Administration has approved Sanofi's Myqorzo (aficamten) for obstructive hypertrophic cardiomyopathy and Redemplo (plozasiran) for familial chylomicronemia syndrome.
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- Both therapies received breakthrough therapy designations and target severe conditions with significant unmet medical needs, potentially transforming treatment options for Chinese patients.
- The approvals strengthen Sanofi's commitment to the Chinese market and expand access to innovative treatments for rare genetic disorders.8 months agoArrowhead Submits Plozasiran NDA to FDA for Familial Chylomicronemia Syndrome- Arrowhead Pharmaceuticals has submitted an NDA to the FDA for plozasiran, targeting familial chylomicronemia syndrome (FCS), a rare genetic disease with no approved treatments.
- The NDA is based on positive Phase 3 PALISADE study results, which showed significant reductions in triglycerides, apolipoprotein C-III, and acute pancreatitis incidence.
- Plozasiran demonstrated an 80% median reduction in triglycerides and an 83% reduction in acute pancreatitis risk compared to placebo in the PALISADE trial.
- Arrowhead plans to submit applications for plozasiran approval to additional regulatory authorities in 2025, expanding its reach to patients beyond the U.S.last yearArrowhead Submits FDA Application for Plozasiran in Familial Chylomicronemia Syndrome- Arrowhead Pharmaceuticals has submitted a New Drug Application (NDA) to the FDA for plozasiran, targeting familial chylomicronemia syndrome (FCS).
- The NDA is based on Phase 3 PALISADE study results, which demonstrated significant triglyceride reductions and decreased acute pancreatitis risk.
- Plozasiran aims to address the unmet need in FCS, a severe genetic disease with currently no FDA-approved treatments.
- The company plans to submit further applications to other regulatory authorities in 2025, expanding plozasiran's potential availability.last yearArrowhead Submits FDA Application for Plozasiran in Familial Chylomicronemia Syndrome- Arrowhead Pharmaceuticals has submitted a New Drug Application (NDA) to the FDA for plozasiran, a potential treatment for familial chylomicronemia syndrome (FCS).
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- Arrowhead plans to submit a New Drug Application to the FDA by the end of 2024, seeking approval for plozasiran as a treatment for FCS, where currently no approved therapies exist.
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