A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Clinical Study to Evaluate the Safety and Efficacy of SAL003 Monotherapy in Participants With Hypercholesterolemia and Mixed Dyslipidemia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 618
- 试验地点
- 1
- 主要终点
- Percent change of Low-Density Lipoprotein Cholesterol (LDL-C).
研究概览
简要总结
This is a Phase 3 study to evaluate the efficacy and safety of SAL003, a fully human monoclonal antibody against PCSK9, as monotherapy in Chinese participants with hypercholesterolemia and mixed dyslipidemia. Participants who are not on lipid-lowering therapy or have washed out from previous therapy will be randomized in a 2:1 ratio to receive either SAL003 140 mg or matching placebo, administered subcutaneously every 4 weeks for 12 weeks. Following the double-blind period, all participants will enter an open-label extension period and receive SAL003 140 mg Q4W for an additional 40 weeks. The primary objective is to demonstrate the superiority of SAL003 over placebo in reducing Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12.
详细描述
This is a multicenter, randomized, double-blind, placebo-controlled, Phase 3 clinical trial. The study consists of four periods: a Screening Period (up to 1 week), a Run-in Period (2 weeks), a Double-blind Treatment Period (12 weeks), and an Extended Treatment Period (40 weeks), with a total study duration of approximately 55 weeks per participant.
Approximately 600 participants will be randomized. Eligible participants must be aged 18-75 years with a fasting LDL-C level between 2.6 mmol/L and 4.9 mmol/L, who are either statin-naïve or have washed out from lipid-lowering drugs for at least 3 months. Key exclusion criteria include familial hypercholesterolemia, established atherosclerotic cardiovascular disease (ASCVD), uncontrolled hypertension, poorly controlled diabetes, and significant hepatic or renal impairment.
In the Double-blind Period, participants will be stratified by baseline LDL-C (<3.4 mmol/L or ≥3.4 mmol/L) and randomized to receive either SAL003 140 mg or placebo via subcutaneous injection every 4 weeks for 3 doses (Days 1, 29, and 57). After completing the 12-week double-blind period, all participants will enter the Extended Treatment Period and receive open-label SAL003 140 mg Q4W for 10 additional doses (from Week 12 to Week 52).
The primary efficacy endpoint is the percent change from baseline in LDL-C at Week 12. Key secondary endpoints include the change from baseline in LDL-C at Week 12, the proportion of participants achieving LDL-C target goals at Week 12 and Week 52, and the percent change from baseline in other lipid parameters (e.g., TC, TG, Non-HDL-C, ApoB) at Week 12 and Week 52. Safety, immunogenicity, and pharmacokinetics will be assessed throughout the study.
The primary analysis will be performed on the Full Analysis Set (FAS) using a repeated measures mixed-effects model (MMRM) to compare the least-squares mean difference between the SAL003 and placebo groups at Week 12.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, aged 18 to 75 years (inclusive).
- •Fasting LDL-C ≥2.6 mmol/L and <4.9 mmol/L at screening/randomization.
- •Meets criteria based on the 2023 Chinese Lipid Management Guidelines (e.g., specific LDL-C levels with certain risk factors, or presence of diabetes).
- •Fasting triglycerides (TG) ≤5.6 mmol/L at screening/randomization.
- •Provides written informed consent.
排除标准
- •Diagnosis of familial hypercholesterolemia (HoFH or HeFH).
- •History of atherosclerotic cardiovascular disease (ASCVD).
- •Uncontrolled hypertension (SBP ≥160 mmHg or DBP ≥100 mmHg).
- •Type 1 diabetes or poorly controlled Type 2 diabetes (HbA1c >8.0%).
- •Significant hepatic or renal impairment.
- •Active liver disease or positive for HIV or Syphilis.
- •History of malignancy within 5 years prior to screening.
- •Use of any lipid-lowering drugs (statins, ezetimibe, etc.) or traditional Chinese medicines known to affect lipid metabolism within 3 months prior to screening.
- •Prior treatment with any PCSK9 inhibitor.
- •Known hypersensitivity to any component of the investigational product or history of severe allergy to antibody therapies.
- •Any other condition deemed by the investigator to be unsuitable for participation.
研究组 & 干预措施
Test Group
Drug: SAL003 140 mg
干预措施: SAL003 140 mg (Drug)
Reference Group
Drug: Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Percent change of Low-Density Lipoprotein Cholesterol (LDL-C).
时间窗: at Week 12
Percent change from baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12.
次要结局
未报告次要终点