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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hyperlipidemia
• Intervention / Treatment: Drug: HRS-7249 Injection; Drug: HRS-7249 Injection

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chanjuan Deng, MM; Phone Number: 0518-82342973; Email: Chanjuan.deng@hengrui.com
• Study Contact Backup: Name: Jianpeng Su, MS; Phone Number: 0518-82342973; Email: jianpeng.su.js18@hengrui.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250014
      • The First Affiliated Hospital of Shandong First Medical University (Qianfo Shan Hospital of shandong province).
      • Principal Investigator: Mei Gao
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200030
      • Shanghai Chest Hospital
      • Principal Investigator: Xumin Hou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; HRS-7249 Injection; Low dose, subcutaneous administration	Drug: HRS-7249 Injection; Dosing level: Low dose; Drug: HRS-7249 Injection; Dosing level: High dose
Experimental: Arm 2; HRS-7249 Injection; High dose, subcutaneous administration	Drug: HRS-7249 Injection; Dosing level: Low dose; Drug: HRS-7249 Injection; Dosing level: High dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with TG<1.7 mmol/L	48 weeks
Proportion of patients with TG<2.3 mmol/L	48 weeks
Proportion of patients with baseline TG≥5.7 mmol/L achieving TG<5.7 mmol/L	48 weeks
Percentage change and absolute value change from baseline in TG	72 weeks
Percentage change and absolute value change from baseline in APOC3	72 weeks
Percentage change and absolute value change from baseline in HDL-C	72 weeks
Percentage change and absolute value change from baseline in TC	72 weeks
Percentage change and absolute value change from baseline in LDL-C	72 weeks
Percentage change and absolute value change from baseline in sdLDL-C	72 weeks
Percentage change and absolute value change from baseline in non-HDL-C	72 weeks
Percentage change and absolute value change from baseline in ApoB	72 weeks
Percentage change and absolute value change from baseline in ApoA1	72 weeks
Percentage change and absolute value change from baseline in Lp(a)	72 weeks
Percentage change and absolute value change from baseline in VLDL-C	72 weeks
Percentage change and absolute value change from baseline in RC	72 weeks
Percentage change and absolute value change from baseline in HbA1c	72 weeks
Incidence rate of acute pancreatitis	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)	72 weeks
Plasma Concentration of long-term HRS-7249 treatment	72 weeks
Dynamics of anti-drug antibody (ADA) following long-term HRS-7249 treatment	72 weeks

Collaborators and Investigators

• Sponsor: Fujian Shengdi Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): October 15, 2028
• Study Completion (Estimated): October 15, 2028

Study Registration Dates

• First Submitted: August 21, 2026
• First Submitted That Met QC Criteria: August 28, 2026
• First Posted (Actual): September 2, 2026

Study Record Updates

• Last Update Posted (Actual): September 2, 2026
• Last Update Submitted That Met QC Criteria: August 28, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Dyslipidemias; Lipid Metabolism Disorders; Nutritional and Metabolic Diseases; Hyperlipidemias
• Other Study ID Numbers: HRS-7249-203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No