| Eligibility |
Inclusion Criteria:
- Men or women aged = 18 years and = 65 years (including boundary values) who signed
informed consent.
Meets the diagnostic criteria for familial hypercholesterolemia. When screening, there are
mutations in the PCSK9 and/or ApoB and/or LDLR genes.
4. When screening, the weight should be = 40kg, and the body mass index (BMI) should be
between 18-30 kg/m2 (including boundary values).
5. During screening, subjects must meet the following laboratory standards: 5.1 Blood
routine: Absolute neutrophil count (ANC) = 1.5 × 109/L, platelet count (PLT) = 100 × 109/L,
hemoglobin count (HGB) = 90 g/dL; 5.2 Liver function: aspartate aminotransferase (AST),
alanine aminotransferase (ALT), alkaline phosphatase (ALP) < 2.0 × ULN, total bilirubin
(TBIL) = 1.5 × ULN; 5.3 Renal function: Serum creatinine (Cr) = 1.5 × ULN, and glomerular
filtration rate (GFR)>60mL/min * 1.73m2; 5.4 Coagulation function: prothrombin time (PT),
activated partial thromboplastin time (APTT), international standardized ratio (INR)<1.5 x
ULN; 5.5 Low density lipoprotein cholesterol (LDL-C) = 4.21mmol/L, and fasting
triglycerides<5.6mmol/L.
6. The subjects and their partners must take effective contraceptive measures during the
participation in this study until 6 months after the end of the main study.
7. The subject must agree not to accept other lipid-lowering drugs for at least 28 days
after receiving the investigational drug.
8. Voluntarily sign informed consent
Exclusion Criteria:
1. Those who have used any prescription drugs that affect blood lipid metabolism within
at least 14 days before receiving the study drug (or within 7 half lives of the drug,
whichever is longer, applicable to small molecule/small nuclear acid drugs) or within
3 months (applicable to biological agents such as PCSK9 inhibitors), or who have used
any over-the-counter drugs that affect blood lipid metabolism within at least 14 days
before receiving the study drug (such as Chinese medicine/traditional Chinese patent
medicines and simple preparations, vitamins, fish oil (>1000mg/day), drugs containing
red koji rice or health products, etc.), (Exception of those who have received stable
non-cyclical hormone replacement therapy for more than 8 weeks and agree not to change
the hormone treatment more than 28 days after the study drug administration);
individuals who have participated in clinical studies of other lipid-lowering drugs
and have accepted the investigational drugs within 6 months before the screening
period.
2. Poorly controlled hypertensive patients who have receive conventional treatments
(systolic blood pressure (SBP) = 160mmHg and/or diastolic blood pressure (DBP) =
100mmHg).
3. Poorly controlled diabetes patients (glycosylated hemoglobin>8.5%).
4. Individuals who are allergic to drugs or mRNA vaccine components contained in lipid
nanoparticles (LNPs), or have experienced adverse reactions to LNP drug therapy, such
as:
4.1 After receiving LNP drug treatment, ALT or AST>3.0 × ULN; 4.2 After receiving LNP
drug treatment, INR>1.5 or APTT/d-dimer>1.5 × ULN; 4.3 Any infusion response that
requires clinical intervention, slows down infusion rate, or stops LNP drugs
treatment; 4.4 Any other adverse reactions that researchers believe are related to the
treatment of LNP drugs.
5. Within three months before the screening, individuals who smoke more than 5 cigarettes
per day or consume an equal amount of nicotine or nicotine substitutes.
6. Individuals with a history of alcohol abuse [consuming more than 14 units of alcohol
per week (1 unit ˜ 360mL of beer or 45mL of 40% liquor or 150mL of wine)] within 3
months before the screening; Individuals positive for alcohol breath test during the
screening or admission.
7. Grade III-IV heart failure defined by the New York Heart Association (NYHA), or left
ventricular ejection fraction<50%, or prolonged QTc interval (>470ms in females
and>450ms in males) found during the screening.
8. Suffering poorly controlled severe arrhythmia , such as recurrent and highly
symptomatic ventricular tachycardia with poorly drug controlled, atrial fibrillation
with rapid ventricular reaction, or supraventricular tachycardia within three months
before the screening.
9. Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary
artery bypass grafting, severe deep vein thrombosis or pulmonary embolism within three
months before the screening; Cerebrovascular accidents occurring within 6 months
before the screening or planning for cardiac surgery or revascularization during the
main study period.
10. Suffering from diseases that have a significant impact on blood lipid levels and
cannot be controlled, such as nephrotic syndrome, severe liver disease, Cushing's
syndrome, thyroid dysfunction, etc. (Individuals with hypothyroidism who have
undergone stable thyroid replacement therapy for = 28 days before screening, have
normal TSH testing, and agree to maintain the dose of thyroid replacement drugs
unchanged during the study can be considered to be enrolled).
11. Individuals who have donated more than 500 mL of blood within three months before
screening.
12. Those who are unable or unwilling to accept the medication treatment required before
the investigational treatment.
13. Patients who underwent antithrombotic treatment (such as warfarin, dabigatran, and
apixaban) within 14 days prior to enrollment.
14. Those who are prone to bleeding or have a history of coagulation disorders (such as
cirrhosis, malignant hematological diseases, antiphospholipid antibody syndrome);
15. Patients with an expected survival period of less than 2 years.
16. Individuals who are known or suspected to have systemic viral, parasitic, or fungal
infections, or are expected to receive antibiotic treatment within 14 days after
screening.
17. Hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (HCV Ab) or human
immunodeficiency virus (HIV) antibody positive during the screening.
18. Individuals who have received liver, heart, or other solid organ transplantation, bone
marrow transplantation within one year before the screening, or having a
transplantation plan during the clinical trial.
19. Individuals with a history of malignant tumors within 5 years before the screening
(excluding curative skin basal cell carcinoma, skin squamous cell carcinoma, cervical
carcinoma in situ, low-grade prostate carcinoma in situ, and curative thyroid basal
carcinoma in situ).
20. Individuals with a history of drug use within three years before the screening.
21. Pregnant or lactating women.
22. Patients with other systemic diseases such as the blood system, digestive system, or
central nervous system (including cerebrovascular diseases and degenerative diseases)
that the researchers believe will interfere with the evaluation or limit the
participation in the trial.
23. Severe mental diseases that researchers believe which cannot be fully controlled by
the medication treatment.
24. Those who are unwilling to follow the research procedures or are unwilling to fully
cooperate.
25. Other situations that researchers believe not suitable to participate in the clinical
trial.
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