HeFH or ASCVD
Conditions
Interventions
Dose escalation group (50 mg):YOLT-101 Injection Therapy(50mg)
Dose escalation group (40 mg):YOLT-101 Injection Therapy(40mg)
Dose Expansion Cohort:After confirming the OBD dose, proceed with an expanded study using the OBD dose of YOLT-101
Sponsors
Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: FH and ASCVD Shared Criteria: 1. Males or females aged >=18 years and =40 kg and body mass index (BMI) >18 kg/m^2 at screening; 3. Subjects must meet the following laboratory criteria at screening: (1) Complete blood count: Absolute neutrophil count (ANC) >=1.5×10?/L, platelets (PLT) >=100×10^9/L, hemoglobin (HGB) >=90 g/L; (2) Liver function: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) 60 mL/min*1.73 m^2; (4) Coagulation function: Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR) =2.6 mmol/L; for ASCVD patients, based on the above treatment and according to the 2023 "Chinese Guidelines for Lipid Management," extremely high-risk patients must have LDL-C >=1.8 mmol/L, and ultra-high-risk patients must have LDL-C >=1.4 mmol/L; 5. Subjects and their partners must use effective contraception from participation in this study until at least 6 months after the end of the main study; 6. Voluntarily sign the informed consent form; FH-Specific Criteria: 7. Meet the diagnostic criteria for familial hypercholesterolemia, or heterozygous mutations in PCSK9, ApoB, or LDLR confirmed at screening; ASCVD-Specific Criteria: 8. Meet the diagnostic criteria for ASCVD.
Exclusion criteria
Exclusion criteria: 1. Patients genetically diagnosed with homozygous FH (HoFH), double heterozygous FH, or compound heterozygous FH; 2. Patients who, within at least 14 days before receiving the study drug (or within 5 half-lives of the drug, whichever is longer, applicable to small molecule drugs), or within 3 months (applicable to biologics such as PCSK9 inhibitors), or within 1 year (PCSK9 small nucleic acid drugs), have used prescribed drugs that affect lipid metabolism other than statins and ezetimibe, or who have used any lipid metabolism-affecting over-the-counter drugs, traditional Chinese herbs/formulations, health products, or nutritional supplements within at least 14 days before receiving the study drug; patients currently participating in other lipid-lowering drug clinical studies and have used the study drug; 3. Patients with poorly controlled hypertension under conventional treatment (systolic blood pressure (SBP) >=160 mmHg and/or diastolic blood pressure (DBP) >=100 mmHg); 4. Patients with poorly controlled diabetes (glycated hemoglobin >8.5%); 5. Patients who, as assessed by the investigator, are allergic to the drugs contained in lipid nanoparticles (LNPs) or components of LNP-mRNA vaccines, or have experienced adverse reactions to LNP-based drugs; 6. Patients who, within 3 months prior to screening, smoked more than 5 cigarettes per day or consumed an equivalent amount of nicotine or nicotine substitutes; 7. Patients who, within 3 months prior to screening, have a history of alcohol abuse [consuming more than 14 units of alcohol per week (1 unit ˜ 360 mL beer, 45 mL 40% spirits, or 150 mL wine)]; or patients who test positive for alcohol on breathalyzer at screening or admission; 8. Patients who, at screening, have New York Heart Association (NYHA) class III-IV heart failure, left ventricular ejection fraction 470 ms, male >450 ms); 9. Patients who, within 3 months prior to screening, have poorly controlled severe arrhythmias, such as recurrent and highly symptomatic ventricular tachycardia poorly controlled by medication, rapid ventricular response atrial fibrillation, or supraventricular tachycardia; 10. Patients who, within 3 months prior to screening, have had myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft surgery, severe deep vein thrombosis or pulmonary embolism; or within 6 months prior to screening, have had a cerebrovascular accident or plan to undergo cardiac surgery or cardiac revascularization during the main study period; 11. Individuals with diseases that significantly affect lipid levels and cannot be controlled, such as nephrotic syndrome, severe liver disease, Cushing's syndrome, thyroid dysfunction, etc. (subjects with hypothyroidism prior to screening who have been on stable thyroid replacement therapy for >=28 days with normal TSH levels and agree to maintain the same dose of thyroid replacement therapy during the study may be considered for enrollment). 12. Those who donated more than 500 mL of blood within 3 months prior to screening; 13. Those who cannot or are unwilling to receive the required medication regimen before treatment; 14. Those who received antithrombotic therapy (such as warfarin, dabigatran, apixaban) within 14 days before enrollment; 15. Individuals with a history of easy bleeding or coagulation disorders (such as cirrhosis, malignant hematologic diseases, antiphospholipid antibody syndrome); 16
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse Events;Vital Signs;Physical Examination;Laboratory tests;12-lead electrocardiogram; | — |
Secondary
| Measure | Time frame |
|---|---|
| Low-density lipoprotein cholesterol; | — |
Countries
China
Contacts
Public ContactXia Qiang
Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Outcome results
None listed