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A Extension Study to Evaluate the Safety and Efficacy of HRS-7249 in Patients With Hypertriglyceridemia

2026年8月28日 更新者:Fujian Shengdi Pharmaceutical Co., Ltd.

A Multi-center, Open-label Extension Study to Evaluate the Long-term Safety and Efficacy of HRS-7249 in Patients With Hypertriglyceridemia

This is a Phase II multi-center, open-label extension (OLE) clinical trial of HRS-7249, a GalNAc-conjugated APOC3-targeted siRNA injection, enrolling two cohorts of participants. Cohort 1 includes subjects who completed parent study HRS-7249-201 within 24 weeks; Cohort 2 newly recruited patients with fasting triglyceride (TG) ≥2.3 mmol/L aged 18-79 years. All participants receive subcutaneous HRS-7249 for a 48-week treatment period followed by a 24-week safety follow-up phase, with two dosing regimens. The primary objective is to assess long-term safety and tolerability of repeated HRS-7249 administration. Secondary objectives include evaluating sustained lipid-lowering effects on TG, APOC3 and other lipid profiles, impacts on glycometabolism, incidence of acute pancreatitis and major adverse cardiovascular events (MACE), long-term pharmacokinetic/pharmacodynamic (PK/PD) profiles, and anti-drug antibody (ADA) dynamics. All safety assessments including vital signs, physical examinations, laboratory tests, 12-lead ECG, injection site reactions and adverse events will be collected throughout the study. Lipid parameters, HbA1c, pancreatitis and cardiovascular events will be monitored to characterize the clinical benefit-risk profile of long-term HRS-7249 therapy in hypertriglyceridemia patients. A total of at least 400 subjects will be enrolled nationwide in China.

研究概览

研究类型

介入性

注册 (估计的)

400

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习联系方式

研究联系人备份

学习地点

    • Shandong
      • Jinan、Shandong、中国、250014
        • The First Affiliated Hospital of Shandong First Medical University (Qianfo Shan Hospital of shandong province).
        • 首席研究员:
          • Mei Gao
    • Shanghai Municipality
      • Shanghai、Shanghai Municipality、中国、200030
        • Shanghai Chest Hospital
        • 首席研究员:
          • Xumin Hou

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

  • 成人
  • 年长者

接受健康志愿者

不

描述

Inclusion Criteria:

- Cohort 1 (Roll-over participants from HRS-7249-201)

  1. Able to understand trial procedures, voluntarily participate and provide written informed consent;
  2. Completed last visit of parent study HRS-7249-201 within 24 weeks prior to screening;
  3. Male or female subjects aged ≥18 and <80 years at consent signature. Cohort 2 (Newly enrolled participants)

1. Able to understand trial procedures, voluntarily participate and provide written informed consent; 2. Fasting triglyceride ≥2.3 mmol/L at screening; 3. Male or female subjects aged ≥18 and <80 years at consent signature.

Exclusion Criteria:

- Cohort 1 Exclusion

  1. Permanently discontinued parent study treatment due to treatment-related adverse events (TRAE);
  2. Persistent clinically significant adverse events or lab abnormalities unresolved by parent study final visit, judged by investigator to increase risk of continued dosing;
  3. Unstable or severe hepatic, renal, cardiovascular, neurological, endocrine, hematologic disorders that render participation unacceptable;
  4. Plan to receive major surgery during study period;
  5. Planned plasmapheresis during trial;
  6. Intend to use weight-loss drugs or undergo weight-altering surgery during trial;
  7. Refuse lifestyle intervention or limit daily alcohol intake below 30 g/day;
  8. Pregnant or breastfeeding females;
  9. Fertile women without contraception within 30 days pre-screening; fertile male/female subjects refusing contraception and gamete donation restrictions through follow-up;
  10. Any other conditions judged unsuitable by investigator. Cohort 2 Exclusion

1. History of acute pancreatitis within 3 months pre-randomization; 2. Plasmapheresis received or planned within 4 weeks pre-randomization; 3. Malignancy diagnosed within past 5 years (except cured non-melanoma skin cancer/cervical carcinoma in situ); 4. NYHA Class III/IV heart failure at screening/randomization; 5. Acute coronary syndrome, stroke, TIA, major cardiovascular revascularization within past 3 months; 6. Severe symptomatic arrhythmia within 3 months pre-randomization; 7. Severe trauma/major surgery within 6 months or planned major operation during trial; 8. Severe infection within past 3 months; 9. Nephrotic syndrome, severe liver disease, Cushing syndrome interfering with lipid metabolism; 10. Unstable severe multi-organ systemic diseases; 11. Uncontrolled hypertension (SBP≥160 mmHg or DBP≥100 mmHg); 12. Plan to take weight-loss agents or bariatric surgery within 2 months pre-screening; 13. Type 1 DM, newly diagnosed DM within 12 weeks, or HbA1c ≥8.5%; 14. Current/history hyper/hypothyroidism; 15. History of substance/alcohol abuse (daily ethanol >80 g); 16. Major lifestyle modification within past 4 weeks or refusal of alcohol/lifestyle limits; 17. eGFR <60 mL/min/1.73m² by MDRD formula; 18. ALT/AST ≥2×ULN; 19. Total/direct bilirubin ≥1.5×ULN; 20. CK >1.5×ULN; 21. Platelet count <100×10⁹/L or thrombocytopenia history; 22. Positive HIV/HCV-Ab, or HBsAg positive with HBV-DNA ≥1000 copies/mL; 23. Participated in other interventional drug trials within 3 months pre-screening; 24. Pregnant or lactating women; 25. Fertile subjects without compliant contraception; 26. Any other conditions deemed inappropriate by investigator.

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:治疗
  • 分配:随机化
  • 介入模型:并行分配
  • 屏蔽:无(打开标签)

武器和干预

参与者组/臂
干预/治疗
实验性的:Arm 1
HRS-7249 Injection; Low dose, subcutaneous administration
Dosing level: Low dose
Dosing level: High dose
实验性的:Arm 2
HRS-7249 Injection; High dose, subcutaneous administration
Dosing level: Low dose
Dosing level: High dose

研究衡量的是什么?

主要结果指标

结果测量
大体时间
Injection site reactions
大体时间:48 weeks
48 weeks
All adverse events (AEs)
大体时间:72 weeks
72 weeks
Respiratory rate
大体时间:72 weeks
72 weeks
Pulse rate
大体时间:72 weeks
72 weeks
Systolic and diastolic blood pressure
大体时间:72 weeks
72 weeks
Body temperature
大体时间:72 weeks
72 weeks
Complete Blood Count
大体时间:72 weeks
72 weeks
Blood chemistry
大体时间:72 weeks
72 weeks
High-sensitivity C-reactive protein (hs-CRP)
大体时间:72 weeks;
72 weeks;
Heart rate
大体时间:72 weeks;
72 weeks;
PR interval
大体时间:72 weeks
72 weeks
QRS duration
大体时间:72 weeks
72 weeks
QT interval
大体时间:72 weeks
72 weeks
QTc interval
大体时间:72 weeks
72 weeks
Urinalysis
大体时间:72 weeks
72 weeks

次要结果测量

结果测量
大体时间
Proportion of patients with TG<1.7 mmol/L
大体时间:48 weeks
48 weeks
Proportion of patients with TG<2.3 mmol/L
大体时间:48 weeks
48 weeks
Proportion of patients with baseline TG≥5.7 mmol/L achieving TG<5.7 mmol/L
大体时间:48 weeks
48 weeks
Percentage change and absolute value change from baseline in TG
大体时间:72 weeks
72 weeks
Percentage change and absolute value change from baseline in APOC3
大体时间:72 weeks
72 weeks
Percentage change and absolute value change from baseline in HDL-C
大体时间:72 weeks
72 weeks
Percentage change and absolute value change from baseline in TC
大体时间:72 weeks
72 weeks
Percentage change and absolute value change from baseline in LDL-C
大体时间:72 weeks
72 weeks
Percentage change and absolute value change from baseline in sdLDL-C
大体时间:72 weeks
72 weeks
Percentage change and absolute value change from baseline in non-HDL-C
大体时间:72 weeks
72 weeks
Percentage change and absolute value change from baseline in ApoB
大体时间:72 weeks
72 weeks
Percentage change and absolute value change from baseline in ApoA1
大体时间:72 weeks
72 weeks
Percentage change and absolute value change from baseline in Lp(a)
大体时间:72 weeks
72 weeks
Percentage change and absolute value change from baseline in VLDL-C
大体时间:72 weeks
72 weeks
Percentage change and absolute value change from baseline in RC
大体时间:72 weeks
72 weeks
Percentage change and absolute value change from baseline in HbA1c
大体时间:72 weeks
72 weeks
Incidence rate of acute pancreatitis
大体时间:72 weeks
72 weeks
Incidence rate of major adverse cardiovascular events (MACE, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina, or coronary revascularization)
大体时间:72 weeks
72 weeks
Plasma Concentration of long-term HRS-7249 treatment
大体时间:72 weeks
72 weeks
Dynamics of anti-drug antibody (ADA) following long-term HRS-7249 treatment
大体时间:72 weeks
72 weeks

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年9月30日

初级完成 (估计的)

2028年10月15日

研究完成 (估计的)

2028年10月15日

研究注册日期

首次提交

2026年8月21日

首先提交符合 QC 标准的

2026年8月28日

首次发布 (实际的)

2026年9月2日

研究记录更新

最后更新发布 (实际的)

2026年9月2日

上次提交的符合 QC 标准的更新

2026年8月28日

最后验证

2026年8月1日

更多信息

与本研究相关的术语

其他研究编号

  • HRS-7249-203

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

未定

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

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