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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
79 Years
Healthy volunteers
No
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.
Primary outcome measure(s)
Injection site reactions — 48 weeks
All adverse events (AEs) — 72 weeks
Respiratory rate — 72 weeks
Pulse rate — 72 weeks
Systolic and diastolic blood pressure — 72 weeks
Body temperature — 72 weeks
Complete Blood Count — 72 weeks
Blood chemistry — 72 weeks
High-sensitivity C-reactive protein (hs-CRP) — 72 weeks；
Heart rate — 72 weeks；
PR interval — 72 weeks
QRS duration — 72 weeks
QT interval — 72 weeks
QTc interval — 72 weeks
Urinalysis — 72 weeks
Trial sites (2)
Facility
City
Region
Status
The First Affiliated Hospital of Shandong First Medical University (Qianfo Shan Hospital of shandong province).
Jinan
Shandong
Shanghai Chest Hospital
Shanghai
Shanghai Municipality
More Fujian Shengdi Pharmaceutical Co., Ltd. trials in China
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time on our Cookie Policy page. See also our Privacy Policy.