NCT05217667终止2 期
Phase 2 Study to Evaluate the Safety and Efficacy of ARO-ANG3 in Subjects With Homozygous Familial Hypercholesterolemia (HOFH)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 18
- 试验地点
- 14
- 主要终点
- Percent Change from Baseline in Fasting Calculated Low-Density Lipoprotein-Cholesterol (LDL-C) and LDL-C by Preparative Ultracentrifugation (LDL-C [PUC]) up to Week 24
研究概览
简要总结
Participants with documented homozygous familial hypercholesterolemia (HoFH) who have provided informed consent will receive 2 open-label doses of ARO-ANG3 and be evaluated for safety and efficacy parameters through 36 weeks. Participants who complete the first 36 week treatment period may opt to continue in an additional 24-month extension period during which they will receive up to 8 doses open-label doses of ARO-ANG3.
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
- None
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Fasting LDL-C >100 mg/dL at Screening
- •Weight of ≥ 40 kg and body mass index ≥ 18.5 and ≤ 40 kg/m2
- •Diagnosis of HoFH based on a supportive genetic test or clinical diagnosis
- •On stable maximally tolerated lipid lowering therapy
- •Willing to abide by stable low-fat, low-cholesterol, heart-healthy diet for at least 4 weeks prior to Day 1
- •Participants of childbearing potential (males & females) must agree to use highly-effective contraception during the study and for at least 24 weeks from the last dose of study medication.
- •Women of childbearing potential must have a negative pregnancy test and cannot be breastfeeding
- •Women of childbearing potential on hormonal contraceptives must be stable on the medications 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 small interfering RNA oligonucleotides (siRNA) or antisense oligonucleoside molecule
- •Use of evinacumab (some exceptions apply)
- •Fasting TG > 300 mg/dL at Screening
- •Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
- •Newly diagnosed (within 3 months prior to informed consent) or poorly controlled diabetes (Hemoglobin A1c > 9%)
- •Use of systemic corticosteroids (some exceptions apply)
- •Symptoms of myocardial ischemia or severe left ventricular dysfunction
- •History of metastatic malignancy within 3 years of Day 1 (some exceptions apply)
- •Planned cardiac procedure/surgery such as coronary artery bypass graft (CABG) surgery, percutaneous coronary intervention (PCI), carotid surgery or stenting, or carotid revascularization
- •Note: additional inclusion/exclusion criteria may apply per protocol
研究组 & 干预措施
ARO-ANG3 Dose 1
Experimental
ARO-ANG3 Dose Level 1 subcutaneous (SC)
干预措施: ARO-ANG 3 Injection (Drug)
ARO-ANG3 Dose 2
Experimental
ARO-ANG3 Dose Level 2 SC
干预措施: ARO-ANG 3 Injection (Drug)
结局指标
主要结局
Percent Change from Baseline in Fasting Calculated Low-Density Lipoprotein-Cholesterol (LDL-C) and LDL-C by Preparative Ultracentrifugation (LDL-C [PUC]) up to Week 24
时间窗: Baseline, up to Week 24
次要结局
- Percent Change from Baseline in Fasting LDL-C (PUC) Over Time(Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period))
- Percent Change from Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) Over Time(Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period))
- Percent Change from Baseline in Fasting Very-Low-Density Lipoprotein-Cholesterol (VLDL-C) Over Time(Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period))
- Absolute Change from Baseline in Fasting LDL-C (PUC) Over Time(Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period))
- Percent Change from Baseline in Fasting Calculated LDL-C Over Time(Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period))
- Absolute Change from Baseline in Fasting Non-HDL-C Over Time(Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period))
- Absolute Change from Baseline in VLDL-C Over Time(Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period))
- Number of Participants with Anti-Drug Antibodies (ADAs) to ARO-ANG3 Over Time(Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period))
- Proportion of Participants meeting United States National Lipid Association Apheresis Eligibility Criteria of LDL-C ≥ 300 mg/dL at Week 24(Week 24)
- Absolute Change from Baseline in Fasting Calculated LDL-C Over Time(Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period))
- Percent Change from Baseline in Fasting Angiopoietin-like 3 (ANGPTL3) Over Time(Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period))
- Absolute Change from Baseline in Fasting Total ApoB Over Time(Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period))
- Absolute Change from Baseline in Fasting HDL-C Over Time(Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period))
- Percent Change from Baseline in Fasting Total Cholesterol (TC) Over Time(Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period))
- Absolute Change from Baseline in Fasting TG Over Time(Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period))
- Absolute Change from Baseline in Fasting ANGPTL3 Over Time(Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period))
- Percent Change from Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) Over Time(Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period) 36)
- Absolute Change from Baseline in Fasting TC Over Time(Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period))
- Number of Participants with Treatment Emergent Adverse Events (TEAEs)(Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period))
- Percent Change from Baseline in Fasting Triglycerides (TG) Over Time(Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period))
- Percent Change from Baseline in Fasting Total Apolipoprotein B (ApoB) Over Time(Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period))
- Proportion of Participants Meeting European Union (EU) Apheresis Eligibility Criteria per German Apheresis Working Group at Week 24(Week 24)
研究者
研究点 (14)
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