familial hypercholesterolemia
Conditions
Interventions
0.2mg/kg Group:YOLT-101 Injection Therapy
0.3mg/kg Group:YOLT-101 Injection Therapy
0.4mg/kg Group:YOLT-101 Injection Therapy
Sponsors
Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Male or female (including boundary values) aged =18 and =65 years old at the time of signing informed consent. 2. Diagnosed with familial hypercholesterolemia according to diagnostic criteria. 3. Presence of PCSK9 and/or ApoB and/or LDLR gene mutation during screening. 4. Weight =40kg and body mass index (BMI) between 18 and 30 kg/m2 (including boundary values) during screening. 5. Subjects must meet the following laboratory criteria during screening: 5.1 Complete blood count: absolute neutrophil count (ANC) =1.5×109/L, platelet count (PLT) =100×109/L, hemoglobin (HGB) =90 g/dL; 5.2 Liver function: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) 60 mL/min*1.73m2; 5.4 Coagulation function: prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR) <1.5×ULN; 5.5 Low-density lipoprotein cholesterol (LDL-C) =3.8 mmol/L and fasting triglycerides <5.6 mmol/L. 6. Subjects and their partners must use effective contraception during the study period and for at least; 6 months after the end of the main study. 7. Subjects must agree not to receive other lipid-lowering medications for at least 28 days after receiving the investigational drug. 8. Voluntarily sign informed consent.
Exclusion criteria
Exclusion criteria: 1. Within at least 14 days before taking the study drug (or within 5 half-lives of the drug, whichever is longer, applicable to small molecule/small nucleic acid drugs) or within 3 months (applicable to biologics such as PCSK9 inhibitors) had used any prescription drugs that affect lipid metabolism, or had used any non-prescription drugs that affect lipid metabolism within at least 14 days before taking the study drug (such as traditional Chinese medicine/patent Chinese medicine, vitamins, fish oil (>1000mg/day), drugs or health products containing red kojic rice component, etc.; (except for those who have been receiving stable non-cyclic hormone replacement therapy for more than 8 weeks and agree not to change the treatment plan for at least 28 days after receiving the investigational drug); currently participating in other lipid-lowering drug clinical studies and have used the study drug. 2. Patients with poorly controlled hypertension (systolic blood pressure (SBP) =160mmHg and/or diastolic blood pressure (DBP) =100mmHg) receiving routine treatment. 3. Patients with poorly controlled diabetes (glycosylated hemoglobin >8.5%). 4. Allergy to the drugs contained in lipid nanoparticles (LNP) or LNP-mRNA vaccines, or had experienced adverse reactions due to the treatment with LNP drugs, for example: 4.1 After treatment with LNP drugs, ALT or AST >3.0×ULN; 4.2 After treatment with LNP drugs, INR >1.5 or APTT/d-dimer>1.5×ULN; 4.3 Any infusion reaction that requires clinical intervention or slowing down or stopping the infusion of LNP drugs; 4.4 Any other adverse reactions considered by the investigator to be related to the treatment with LNP drugs. 5. Smoking more than 5 cigarettes per day or consuming the equivalent amount of nicotine or nicotine replacement products within the past 3 months before screening. 6. History of alcohol abuse within the past 3 months before screening [drinking more than 14 units of alcohol per week (1 unit ˜ 360mL beer or 45mL of 40% alcohol or 150mL wine)]; or positive alcohol breath test at the time of screening or admission. 7. Presence of New York Heart Association (NYHA) class III-IV heart failure, left ventricular ejection fraction 470ms, male >450ms) at the time of screening. 8. Poorly controlled severe arrhythmias within the past 3 months before screening, such as poorly controlled recurrent and highly symptomatic ventricular tachycardia, rapid ventricular response atrial fibrillation, or supraventricular tachycardia. 9. Within the past 3 months before screening, history of myocardial infarction, unstable angina pectoris, percutaneous coronary intervention, coronary artery bypass grafting, severe deep vein thrombosis or pulmonary embolism; within the past 6 months before screening, occurrence of cerebrovascular accidents or planned cardiac surgery or cardiac revascularization during the main study period. 10. Patients with diseases that have a significant impact on lipid levels and cannot be controlled, such as nephrotic syndrome, severe liver disease, Cushing's syndrome, thyroid dysfunction, etc. (Patients with hypothyroidism before screening who have received stable thyroid replacement therapy for =28 days, with normal TSH levels and agree to maintain the same dose of thyroid replacement medication during the study may be considered for inclusion). 11. Blood donation exceeding 500 mL within the past 3 months before screening. 12. Patients who cannot or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse events; vital signs;physical examination;laboratory examination(Blood routine, blood biochemistry, coagulation function, urine routine);Pregnancy examination;12 lead electrocardiogram;Immunogenicity testing; | — |
Secondary
| Measure | Time frame |
|---|---|
| PK indicators include but are not limited to maximum blood drug concentration (Cmax), time to reach;PD index: rate of change in plasma PCSK9 protein level compared to baseline.;Efficacy indicators: changes in low-density lipoprotein cholesterol (LDL-C) levels from baseline; ch; | — |
Countries
China
Contacts
Public ContactXia Qiang
Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine
Outcome results
None listed