A Randomized, Double-blind, Placebo-controlled Phase 3 Clinical Study to Evaluate the Efficacy and Safety of HST101 in Chinese Patients with Hypercholesterolemia
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 210
- 试验地点
- 18
- 主要终点
- LDL-C change compared to Placebo
研究概览
简要总结
This randomized study is to assess LDL-C reductions at Week 12 with monthly (Q4W [≤31 days]) dosing of HST101 (lerodalcibep) 300 mg administered subcutaneously (SC) compared to placebo in patients with atherosclerotic cardiovascular disease (ASCVD) or very-high/high risk for ASCVD including Heterozygous familial hypercholesterolemia (HeFH) on a stable diet and oral LDL-C lowering drug therapy, followed by 36-week open-label treatment with subsequent 4-week follow-up for total 52-week long-term safety and efficacy evaluation.
详细描述
This is a multi-center, randomized, double-blind, placebo-controlled Phase 3 study. Participants who fulfill the inclusion and exclusion criteria will be enrolled at up to 35 study sites in mainland China.
All eligible participants will be randomized in a 2:1 ratio to HST101 or placebo dosed subcutaneously (Q4W [≤31 days]) in the initial 12-week randomized double-blind treatment period. After 12-week treatment, all the participants will enter to the 36-week open-label treatment period where those who are on HST101 will continue to receive HST101 in the same dosing regimen as dosed in the randomized period, and those who are on placebo will be switched to HST101 300 mg (Q4W [≤31 days]) administered subcutaneously.
The total study duration will be up to 55 weeks which includes a up to 3-week Screening Period, 12-week randomized, double-blind, placebo-controlled treatment period, 36-week open-label treatment period, followed by a 4-week follow-up period.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
This study consists of the preceding 12-week double-blind, placebo-controlled treatment period and the subsequent 40-week (incluing 36-week HST101 treatment and 4-week follow-up) open-label treatment period.
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
- •Provision of written and signed informed consent form prior to any study-specific procedure;
- •Male or female participants ≥18 years of age at the screening visit;
- •Body weight ≥ 40 kg and body mass index (BMI) ≥18 and ≤35 kg/m2;
- •On a stable diet and lipid-lowering oral drugs (such as statins, ezetimibe or Hybutimibe, omega-3 compounds, fenofibrate, nicotinic acid, etc.) for at least 4 weeks prior to the first drug administration
- •LDL-C≥1.8 mmol/L (70 mg/dL) and TG≤4.52 mmol/L (400 mg/dL) at screening for ASCVD patients or those at very (ultra)-high risk for ASCVD, including patients with HeFH; LDL-C ≥ 2.6 mmol/L (100 mg/dL) and TG ≤ 4.52 mmol/L (400 mg/dL) at screening for patients at high-risk for ASCVD including patients with HeFH;
- •Patients on a PCSK9 mAb at a dose of 75 mg, 140 mg, or 150 mg Q2W must undergo a washout period of ≥6 weeks after the last dose; for those on 300 mg or 420 mg Q4W, the washout period is ≥10 weeks following last dose;
- •Female of childbearing potential must have a negative pregnancy test at the last screening visit and consent to use highly effective contraceptives during the trial and 3 months after the last dose of investigational drug.
排除标准
- •Documented history of homozygous familial hypercholesterolemia (HoFH);
- •Estimated glomerular filtration rate (eGFR)<30 mL/min/1.73m2;
- •Active liver disease or hepatic dysfunction, history of liver transplant, and/or ALT or AST >2.5 × ULN at screening;
- •Poorly controlled thyroid disorder including hypothyroidism or hyperthyroidism;
- •Poorly controlled Type 1 or Type 2 diabetes mellitus defined as fasting blood glucose ≥11.0 mmol/L (200 mg/dL) and glycosylated hemoglobin (HbA1c) ≥ 9%;
- •Serious arrhythmia, MI, unstable angina pectoris, PCI, CABG, implantable cardioverter defibrillator, aortic valve surgery or stroke within 3 months prior to the first dose;
- •Planned cardiac surgery or revascularization during the study period;
- •New York Heart Association (NYHA) Class III-IV heart failure;
- •Pregnant or lactating women;
- •Poorly controlled hypertension (SBP≥160 mmHg or DBP≥100 mmHg in a sitting position)
- •Unexplained creatine kinase (CK) > 5 x ULN (retested once is needed if suspected to be related to excessive exercise or abnormal activity);
- •LDL apheresis or plasma exchange within 2 months prior to the first dose;
- •HIV, Treponema pallidum, or HCV antibody test positive, or HBV-DNA >ULN at screening;
- •History of prescription drug abuse, illicit drug use or alcohol abuse within 6 months prior to screening;
- •History of any major drug allergy, including allergy to protein biologics;
- •Participate another clinical trial within 30 days or less than 5 half-lifes (drug) before screening, whichever is longer
研究组 & 干预措施
HST101(Lerodalcibep)
300 mg subcutaneously Q4W
干预措施: Lerodalcibep (Drug)
Placebo
subcutaneously Q4W
干预措施: matching placebo (Drug)
结局指标
主要结局
LDL-C change compared to Placebo
时间窗: 12 weeks
Percent change in LDL-C level from baseline (calculated by Friedewald formula) compared to Placebo
Mean LDL-C change at Weeks 10 and 12 compared to Placebo
时间窗: 12 weeks
Percent change in mean LDL-C level from baseline (calculated by Friedewald formula) compared to placebo at Weeks 10 and 12
次要结局
- Percentage of patients achieving LDL-C goals recommended by 2023 Chinese guideline(12 weeks)
- Other Lipid parameters change(12 weeks)
- LDL-C change over time(12 weeks)
- Free PCSK9 change(12 weeks)
- Incidence of treatment-emergent adverse events(52 weeks)