A Multicentre, Randomized, Double-Blind, Placebo-controlled Phase II Clinical Study to Evaluate the Efficacy and Safety of DNV001 Injection at Different Dosages in Patients With Primary Hypercholesterolaemia or Mixed Hyperlipidaemia and Elevated Low Density Lipoprotein Cholesterol (LDL-C) Inadequate
概览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- Hangzhou Dinovate Biotech Co., Ltd
- 入组人数
- 120
- 主要终点
- To evaluate the efficacy of DNV001 in subjects with primary hypercholesterolaemia or mixed hyperlipidaemia with elevated LDL-C levels
概览
简要总结
This is a Phase II clinical study to evaluate the effectiveness and safety of different doses of DNV001 injection in patients with primary hypercholesterolemia or mixed dyslipidemia who have not achieved adequate control of low-density lipoprotein cholesterol (LDL-C) despite statin therapy.
The study will enroll approximately 120 participants and will be conducted at 10-15 centers in China. Participants will be randomly assigned to one of four dose groups (50 mg, 150 mg, 300 mg-1, or 300 mg-2) or placebo, administered as subcutaneous injections. The study includes a 2-week screening period, a 4-week run-in period, a 36-week double-blind treatment period, and a 12-week follow-up period, for a total of up to 54 weeks.
The main goal is to see how much DNV001 lowers LDL-C levels after 24 weeks of treatment. The study will also look at long-term effectiveness, safety, how the body processes the drug, and whether it causes an immune response.
All participants will continue taking their stable dose of statin medication throughout the study.
详细描述
Study Title:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Study to Evaluate the Efficacy and Safety of Different Doses of DNV001 Injection in Patients with Primary Hypercholesterolemia or Mixed Dyslipidemia with Elevated LDL-C Despite Statin Therapy.
Sponsor:
Hangzhou Dinovate Biotech Co., Ltd.
Protocol Number:
DNV001-201
Phase:
Phase II
Study Design:
This is a randomized, double-blind, multicenter, placebo-controlled study. Eligible participants will be assigned in a 1:1:1:1 ratio to one of four dose groups: 50 mg, 150 mg, 300 mg-1, or 300 mg-2. Within each dose group, participants will be further randomized 4:1 to receive either DNV001 or placebo. Each dose group will include 24 participants receiving active drug and 6 receiving placebo, for a total of approximately 96 active and 24 placebo participants.
Study Duration:
Each participant will be involved for up to 54 weeks, including:
- Screening: 2 weeks
- Run-in: 4 weeks
- Double-blind treatment: 36 weeks
- Follow-up: 12 weeks
Key Eligibility Criteria:
Inclusion:
- Adults ≥18 years with primary hypercholesterolemia or mixed dyslipidemia
- Inadequate LDL-C control despite stable statin therapy
- Fasting LDL-C ≥70 mg/dL (with ASCVD history) or ≥100 mg/dL (without ASCVD history)
- Fasting triglycerides ≤400 mg/dL
- Willing to comply with study visits and lifestyle/dietary guidelines
Exclusion:
- Homozygous familial hypercholesterolemia
- Recent major cardiovascular event or procedure
- Uncontrolled hypertension, diabetes, or thyroid disease
- Significant liver, kidney, or heart disease
- Use of other lipid-lowering therapies (except stable statins)
- Recent participation in another clinical trial
Endpoints:
Primary:
· Percent change in LDL-C from baseline at Week 24.
Secondary:
- Percent change in LDL-C at other timepoints up to Week 48
- Proportion of participants achieving LDL-C reduction ≥50%, LDL-C <70 mg/dL, etc.
- Safety (adverse events, lab abnormalities, ECG, vital signs)
- Pharmacodynamics (PCSK9, lipids, lipoproteins)
- Pharmacokinetics (Cmax, Tmax, AUC)
- Immunogenicity (anti-drug antibodies)
Intervention:
DNV001 or matching placebo will be administered subcutaneously in the abdomen, upper arm, or thigh. Dosing schedules vary by group (e.g., 50 mg group: doses at Day 1, Week 12, Week 36; 300 mg-2 group: Day 1 and Week 24).
Statistical Methods:
Analyses will be performed on the Full Analysis Set, Per Protocol Set, and Safety Set. The primary endpoint will be analyzed using a mixed model for repeated measures. Safety and other endpoints will be summarized descriptively.
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)
盲法说明
This is a double-blind study where both the participants and the investigators (including site personnel involved in treatment administration and clinical evaluation) are masked to treatment assignment. The placebo is matched in packaging, and administration to maintain blinding. The sponsor's clinical and monitoring staff are also masked. Unblinding may occur only in medical emergencies per the study protocol. An independent unblinded pharmacist,nurses or designated staff at each site will handle randomization and drug dispensing to maintain allocation concealment.
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
- •Subjects must meet all of the following criteria to be eligible for inclusion in this study:
- •Male or female, aged ≥18 years at the time of signing the informed consent form;
- •Diagnosed with primary hypercholesterolaemia or mixed hyperlipidaemia at screening; have been receiving statin therapy prior to screening; and agree to maintain stable statin therapy (i.e., no change in type or dosage, except for safety reasons) throughout the study;
- •Fasting LDL-C levels at both the screening and run-in periods must meet the following criteria, as tested by a local laboratory: For subjects with a documented history of ASCVD, fasting LDL-C must be ≥ 70 mg/dL (1.8 mmol/L). For subjects without a documented history of ASCVD, fasting LDL-C must be ≥ 100 mg/dL (2.6 mmol/L);
- •Fasting TG ≤ 4.52 mmol/L (400 mg/dL), as tested by a local laboratory, at both the screening and run-in periods;
- •Understand the study procedures and methods, voluntarily agree to participate in this study, be willing to comply with the visit schedule and protocol requirements, and provide written informed consent;
- •Be willing to adhere to the lifestyle requirements specified in the study protocol (including diet and physical activity level) during the study;
- •Female subjects of childbearing potential (WOCBP) and male subjects who have not undergone vasectomy must agree to use a reliable method of contraception during the study and 6 months after study completion or discontinuation; female subjects of childbearing potential must present negative for blood human chorionic gonadotropin (hCG) pregnancy test result at the screening visit and the baseline visit prior to the first dose; male subjects must not donate sperm during the study and for 6 months after study completion or discontinuation.
排除标准
- •Subjects who meet any of the following criteria will not be enrolled in the study:
- •Diagnosed with homozygous familial hypercholesterolaemia prior to screening;
- •Assessed as having an ultra-high risk for overall ASCVD at screening and have undergone percutaneous coronary intervention within 1 year prior to screening;
- •Have other diseases that significantly affect blood lipid levels (such as nephrotic syndrome, severe liver diseases) or have dyslipidemia due to other secondary causes (such as drug-induced dyslipidemia);
- •History of allergy to drugs or foods (two or more), or a history of specific allergic diseases (such as asthma, urticaria, eczematous dermatitis, etc.), or known allergy to any active ingredient or excipient of the investigational product;
- •History of malignancy within the past 5 years (except for cured basal cell carcinoma of the skin, etc.), or currently being evaluated for a potential malignancy;
- •Office blood pressure measurement during the screening and run-in periods: systolic blood pressure (SBP) ≥ 180 mmHg or diastolic blood pressure (DBP) ≥ 110 mmHg (a repeat measurement is permitted, which must be completed on the same day, and no pharmacological intervention is allowed before the repeat measurement);
- •History of serious cardiovascular or cerebrovascular diseases (such as hypertensive encephalopathy, acute stroke, transient ischemic attack, acute myocardial infarction, severe arrhythmia), or severe aortic and/or peripheral vascular diseases (such as abdominal aortic aneurysm, lower limb arteriosclerosis obliterans), or presence of indications for surgical intervention within 6 months prior to screening or during the run-in period;
- •Underwent major surgery within 6 months prior to screening or during the run-in period, or plan to undergo major surgery during the study period;
- •History of New York Heart Association (NYHA) class III-IV heart failure, with a left ventricular ejection fraction (LVEF) \< 40% at screening or run-in period;
研究组 & 干预措施
DNV001-50 mg
Participants receive DNV001 50 mg via subcutaneous injection at Day 1, Week 12, and Week 36, while continuing their stable background statin therapy.
干预措施: DNV001 Injection (Biological)
DNV001-150 mg
Participants receive DNV001 150 mg via subcutaneous injection at Day 1, Week 12, and Week
干预措施: DNV001 Injection (Biological)
DNV001-300-1 mg
Participants receive DNV001 300 mg via subcutaneous injection at Day 1, Week 12, and Week 36, while continuing their stable background statin therapy.
干预措施: DNV001 Injection (Biological)
DNV001-300-2 mg
Participants receive DNV001 300 mg via subcutaneous injection at Day 1 and Week 24 (only two doses), while continuing their stable background statin therapy.
干预措施: DNV001 Injection (Biological)
Placebo
Participants receive matching placebo via subcutaneous injection according to the schedule of the DNV001 dose group to which they are randomized (e.g., at Day 1, Week 12, and Week 36 for the 50 mg, 150 mg, and 300 mg-1 groups; or at Day 1 and Week 24 for the 300 mg-2 group), while continuing their stable background statin therapy.
干预措施: Placebo (Biological)
结局指标
主要结局
To evaluate the efficacy of DNV001 in subjects with primary hypercholesterolaemia or mixed hyperlipidaemia with elevated LDL-C levels
时间窗: Baseline to Week 24
Percent change from baseline in LDL-C levels at Week 24 (W24).
次要结局
- To evaluate other efficacy measures of DNV001 in subjects with primary hypercholesterolaemia or mixed hyperlipidaemia with elevated LDL-C levels(Baseline to Week 48)
- To evaluate the safety of DNV001 in subjects with primary hypercholesterolaemia or mixed hyperlipidaemia with elevated LDL-C levels(Baseline to Week 48)
- To characterize the pharmacodynamics (PD) of DNV001 in subjects with primary hypercholesterolaemia or mixed hyperlipidaemia with elevated LDL-C levels(Baseline to Week 48)
- To characterize the pharmacokinetics (PK) of DNV001 in subjects with primary hypercholesterolaemia or mixed hyperlipidaemia with elevated LDL-C levels(Baseline to Week 48)
- To evaluate the immunogenicity of DNV001.(Baseline to Week 48)