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.
Able to understand trial procedures, voluntarily participate and provide written informed consent;
Completed last visit of parent study HRS-7249-201 within 24 weeks prior to screening;
Male or female subjects aged ≥18 and <80 years at consent signature. Cohort 2 (Newly enrolled participants)
Permanently discontinued parent study treatment due to treatment-related adverse events (TRAE);
Persistent clinically significant adverse events or lab abnormalities unresolved by parent study final visit, judged by investigator to increase risk of continued dosing;
Unstable or severe hepatic, renal, cardiovascular, neurological, endocrine, hematologic disorders that render participation unacceptable;
Plan to receive major surgery during study period;
Parallel
HRS-7249 Injection
DrugDosing level: Low dose
HRS-7249 Injection
DrugDosing level: High dose
Injection site reactions
All adverse events (AEs)
Respiratory rate
Pulse rate
Proportion of patients with TG<1.7 mmol/L
Proportion of patients with TG<2.3 mmol/L
Proportion of patients with baseline TG≥5.7 mmol/L achieving TG<5.7 mmol/L
Percentage change and absolute value change from baseline in TG
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