A Randomized, Double-Blind, Placebo-Controlled, Single-Center Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a Single Dose of HST101 in Healthy Chinese Study Participants With Elevated LDL-C Levels
试验速览
- 阶段
- 1 期
- 状态
- Enrolling By Invitation
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- The primary objective of this study is to assess the safety and tolerability of a single SC dose of HST101 in Chinese healthy adult study participants with elevated LDL-C level(International Standard Unit: mmol/L)
研究概览
简要总结
This is a single-center, randomized, double-blind, placebo-controlled, single HST101 SC dose cohort study to evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Chinese Participants with Elevated LDL-C Levels.
详细描述
The planned 30 study participants will be assigned to low- or high-dose 2 cohorts and 15 participants in each cohort will be randomized to either the HST101 group or the matching dose placebo group and will be administered in subsequent or in-parallel manner. Cohort 1: 15 study participants will receive the low dose of HST101 or placebo at a corresponding dose. Cohort 2: additional 15 study participants will receive the high dose of HST101 or placebo at a corresponding dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Men and women who are ≥18 and ≤55 years of age with elevated LDL-C Levels;
- •LDL-C ≥ 2.6 mmol/L (100 mg/dL) and ≤ 4.9 mmol/L (190 mg/dL) and TG ≤ 2.83 mmol/L (250 mg/dL) who are not on a lipid-lowering therapy 30 days prior to screening;
- •Body mass index (BMI) ≥18 and≤28 kg/m2
排除标准
- •Positive blood screen for HIV antibody, Treponema pallidum antibody, HBsAg or HCV antibody;
- •Clinically significant liver function test abnormalities at screening, such as AST or ALT > 2 × ULN, total bilirubin > 1.5 × ULN, or ALP > 2 × ULN based on normal values;
- •CK > 3 × ULN at the screening visit, it can be retested if considered to be related to exercise;
- •History of prescription drug abuse, illicit drug use or alcohol abuse;
- •Use of any prescription drug, herbal and compound decoction, vitamins, minerals, and OTC drugs and nutritional supplements that alter lipid metabolism within 14 days prior to Check-in and planned use of the above drugs throughout the study;
- •Prior treatment with PCSK9 inhibitors, including mAbs, siRNA products, or any Adnectin products;
- •History of allergy to protein-based biologics including, but not limited to, mAbs and vaccine;
- •Less than 30 days or less than 5 half-lives (drug) since the end of participation in another clinical trial (drug or device), whichever is longer;
- •Use of any other biologics within 3 months prior to investigational product administration;
- •Any other significant clinical diseases or psychological diseases that the investigator considers to be inappropriate for participation in this study.
研究组 & 干预措施
Experimental: cohort low dose HST101
HST101 single SC administration of 150 mg or placebo;
干预措施: HST101 (Drug)
Experimental: cohort high dose HST101
HST101 single SC administration of 300 mg or placebo.
干预措施: HST101 (Drug)
结局指标
主要结局
The primary objective of this study is to assess the safety and tolerability of a single SC dose of HST101 in Chinese healthy adult study participants with elevated LDL-C level(International Standard Unit: mmol/L)
时间窗: 57 days
Safety and tolerability will be assessed by the incidence and severity of treatment emergent adverse events
次要结局
- To assess the pharmacokinetic characteristics and dose proportionality relathionship of HST101 following a single SC dose(57 days)
- To assess the PD effect of a single SC dose of HST101 on serum unbound (free) PCSK9 concentrations and serum LDL-C concentrations(57 days)
- To assess the effect of a single SC dose of HST101 on blood lipids including TC, HDL-C, VLDL-C, and TG(57 days)
- To assess the effect of a single SC dose of HST101 on serum ApoB, Apo A1 concentrations(57 days)
- To assess the effect of a single SC dose of HST101 on serum Lp(a) concentrations(57 days)
- To assess the PK-PD relationship following a single SC dose of HST101(57 days)
- To assess immunogenicity (incidence, titer, and duration of ADAs/NAbs) following a single SC dose of HST101(57 days)