A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Trial to Evaluate the Efficacy and Safety of DR10624 in Subjects With Severe Hypertriglyceridemia Receiving Stable Lipid-Modifying Therapy
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 480
- 试验地点
- 1
- 主要终点
- Percentage change from baseline in central laboratory-measured fasting serum triglyceride at Week 26
研究概览
简要总结
This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial to assess the efficacy and safety of weekly subcutaneous DR10624 injection in adult patients with severe hypertriglyceridemia (sHTG). Eligible participants have persistently elevated fasting triglycerides despite stable background lipid-lowering therapy. Subjects will be randomized at a 2:2:1 ratio to three treatment arms: DR10624 low dose, DR10624 high dose, or matching placebo, receiving weekly subcutaneous injections for a total of 64 weeks double-blind treatment, followed by a 4-week post-treatment safety follow-up. The primary goal is to evaluate the percentage reduction in fasting triglycerides at Week 26. Secondary assessments include changes in ApoC3, remnant cholesterol, liver fat content measured by MRI-PDFF, incidence of adjudicated acute pancreatitis, and overall safety profile including treatment-emergent adverse events and immunogenicity.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged ≥18 years at screening.
- •BMI 19.0-45.0 kg/m², body weight ≥50.0 kg.
- •Fasting triglyceride meets protocol-specified threshold at local lab and average of two separate central lab fasting samples collected ≥1 week apart.
- •On stable guideline lipid-lowering therapy ≥4 weeks.
- •Able to follow protocol and maintain stable lifestyle; sign voluntary written informed consent.
排除标准
- •Confirmed/suspected familial severe hypertriglyceridemia subtypes (Fredrickson Type 1/3, ApoC-II deficiency).
- •Unstable body weight, severe liver/kidney disease, uncontrolled diabetes or hypertension, NYHA III-IV heart failure, Cushing syndrome.
- •History of acute pancreatitis within 6 months, chronic pancreatitis or symptomatic gallbladder disease.
- •Recent major cardiovascular events, bone disorders, abnormal thyroid function or active malignancy within 5 years.
- •Severe psychiatric disorders, substance abuse/excessive alcohol intake, or MTC/MEN2 family/personal history.
- •Prior exposure to GLP-1R/GCGR/FGF21R agonists, relevant investigational drugs or other interventional trials within 3 months.
- •Unqualified lab results at screening: abnormal liver/pancreas/renal indexes, elevated HbA1c, positive HIV/HBV/HCV, severe arrhythmia.
- •Pregnancy/lactation, contraception refusal, hypersensitivity to study drug, blood donation ≥400mL recently, or any conditions judged by investigator to affect trial safety/efficacy.
研究组 & 干预措施
Dose 1 DR10624 Group
Subcutaneous injection of DR10624 once weekly.
干预措施: DR10624 Injection (Biological)
Dose 2 DR10624 Group
Subcutaneous injection of DR10624 once weekly.
干预措施: DR10624 Injection (Biological)
Placebo Group
Subcutaneous injection of placebo once weekly.
干预措施: Matching Placebo for DR10624 (Other)
结局指标
主要结局
Percentage change from baseline in central laboratory-measured fasting serum triglyceride at Week 26
时间窗: Baseline to Week 26 of double-blind treatment
次要结局
- Percentage change from baseline in central laboratory-measured non-high-density lipoprotein cholesterol (non-HDL-C) at Week 26(Baseline to Week 26 double-blind treatment)
- Proportion of participants achieving fasting triglyceride <5.65 mmol/L at Week 26(Week 26)
- Percentage change from baseline in central laboratory-measured triglyceride-rich lipoprotein cholesterol (TRL-C) at Week 26(Baseline to Week 26 double-blind treatment)
- Percentage change from baseline in central laboratory-measured apolipoprotein C3 (ApoC3) at Week 26(Baseline to Week 26 double-blind treatment)
- Proportion of participants achieving fasting triglyceride <1.70 mmol/L at Week 26(Week 26)
- Percentage change from baseline in liver fat content quantified by blinded central MRI-PDFF imaging at Week 26(Baseline to Week 26 double-blind treatment)
- Cumulative proportion of participants with Event Adjudication Committee (EAC)-confirmed acute pancreatitis from randomization through Week 64(Randomization through Week 64 double-blind treatment)
- Overall incidence and maximum severity grade of all treatment-emergent adverse events (TEAEs)(First study drug injection through 4-week post-treatment safety follow-up)