Early-phase Clinical Study on Safety, Tolerability and Preliminary Efficacy of ART002g1 Injection in the Treatment of Heterozygous Familial Hypercholesterolemia
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
研究概览
简要总结
This study is an open-label, single ascending dose (SAD) study designed to evaluate the safety and tolerability of ART002g1 in patients with heterozygous familial hypercholesterolemia (HeFH) who require further reduction in low-density lipoprotein cholesterol (LDL-C). ART002g1 uses base editing technology, which is designed to interfere with the expression of the PCSK9 gene in the liver, thereby reducing the circulating levels of PCSK9 and LDL-C. The primary objectives of this study are to determine the safety and pharmacodynamic (PD) profiles of ART002g1 in this patient population.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must meet all the following criteria to be eligible for enrollment:
- •Male or female, aged 18 to 70 years (inclusive) at the time of signing the Informed Consent Form (ICF);
- •Body weight between 45 and 90 kg (inclusive) at screening;
- •Definite diagnosis of heterozygous familial hypercholesterolemia (HeFH), meeting either of the following two criteria (1) or (2):
- •（1) HeFH diagnosed to be caused by mutations in the LDLR, APOB, or PCSK9 gene;
- •(2) Meeting 2 out of the 3 following criteria for adults per the Dutch Lipid Clinical Network (DLCN) criteria:
- •Serum LDL-C ≥ 4.7 mmol/L without prior lipid-lowering treatment;
- •Cutaneous or tendinous xanthomas, or arcus cornealis (in subjects < 45 years old);
- •Presence of FH or early-onset atherosclerotic cardiovascular disease (ASCVD) in first-degree relatives.
- •Subjects must not be enrolled if they meet any one or more of the following
排除标准
- •Diagnosis of compound heterozygous FH, double heterozygous FH, or homozygous FH (HoFH);
- •Positive for hepatitis B surface antigen (HBsAg), or positive for hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA titer ≥ 1 × 10² copies/L; positive for hepatitis C virus (HCV) antibody with positive peripheral blood HCV RNA; positive for human immunodeficiency virus (HIV) antibody;
- •Any unstable systemic disease, including but not limited to: unstable angina; cerebrovascular accident or transient ischemic attack (within 6 months prior to screening); myocardial infarction (within 6 months prior to screening); history of heart failure (NYHA Class II-IV); severe arrhythmia requiring pharmacotherapy; liver, kidney, or metabolic diseases; or other unstable systemic diseases as determined by the investigator;
- •History of percutaneous transluminal coronary angioplasty (PTCA), percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG) within 6 months prior to the first dose; or documented severe coronary artery stenosis as confirmed by coronary CT or coronary angiography within 90 days prior to randomization.
研究组 & 干预措施
Experimental: ART002g1 Injection - Dose Group 2 (Single IV Infusion)
Participants will receive a single dose of ART002g1.
干预措施: ART002g1 Injection (Drug)
Experimental: ART002g1 Injection - Dose Group 1 ( Single IV Infusion)
Participants will receive a single dose of ART002g1.
干预措施: ART002g1 Injection (Drug)
Experimental: ART002g1 Injection - Extended Dose Group ( Single IV Infusion)
Participants will receive a single Optimal Biological Dose (OBD) of ART002g1, which is based on the results of the ascending dose escalation.
干预措施: ART002g1 Injection (Drug)
结局指标
主要结局
Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
时间窗: As of Week 48 (W48) post-administration of ART002g1 for Injection
次要结局
- Pharmacokinetic (PK) Assessments: PK Parameters of ART002g1: Tmax(As of Week 2 (W2) post-administration of ART002g1 for Injection)
- Pharmacodynamic (PD) Assessments: Serum PCSK9 protein(As of Week 48 (W48) post-administration of ART002g1 for Injection)
- Pharmacokinetic (PK) Assessments: PK Parameters of ART002g1: Cmax(As of Week 2 (W2) post-administration of ART002g1 for Injection)
- Pharmacokinetic (PK) Assessments: PK Parameters of ART002g1: AUC(As of Week 2 (W2) post-administration of ART002g1 for Injection)
- Pharmacokinetic (PK) Assessments: PK Parameters of ART002g1: t½(As of Week 2 (W2) post-administration of ART002g1 for Injection)
- Pharmacokinetic (PK) Assessments: PK Parameters of ART002g1: CL(As of Week 2 (W2) post-administration of ART002g1 for Injection)
- Pharmacokinetic (PK) Assessments: PK Parameters of ART002g1:Vss(As of Week 2 (W2) post-administration of ART002g1 for Injection)
- Pharmacodynamic (PD) Assessments: Serum LDL-C(As of Week 48 (W48) post-administration of ART002g1 for Injection)
研究者
Rong Jiang
Associate Chief Physician
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine