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

28 augusti 2026 uppdaterad av: 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.

Studieöversikt

Status

Har inte rekryterat ännu

Betingelser

Studietyp

Interventionell

Inskrivning (Beräknad)

400

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studiekontakt

Studera Kontakt Backup

Studieorter

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

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

  • Vuxen
  • Äldre vuxen

Tar emot friska volontärer

Nej

Beskrivning

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.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Arm 1
HRS-7249 Injection; Low dose, subcutaneous administration
Dosing level: Low dose
Dosing level: High dose
Experimentell: Arm 2
HRS-7249 Injection; High dose, subcutaneous administration
Dosing level: Low dose
Dosing level: High dose

Vad mäter studien?

Primära resultatmått

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

Sekundära resultatmått

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

Samarbetspartners och utredare

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Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Beräknad)

30 september 2026

Primärt slutförande (Beräknad)

15 oktober 2028

Avslutad studie (Beräknad)

15 oktober 2028

Studieregistreringsdatum

Först inskickad

21 augusti 2026

Först inskickad som uppfyllde QC-kriterierna

28 augusti 2026

Första postat (Faktisk)

2 september 2026

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

2 september 2026

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

28 augusti 2026

Senast verifierad

1 augusti 2026

Mer information

Termer relaterade till denna studie

Andra studie-ID-nummer

  • HRS-7249-203

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