heterozygous familial hypercholesterolaemia
Conditions
Interventions
Dose-escalation group 5:ART002: 1.5mg/kg, single administration
Dose expansion group:ART002: OBD, single administration
Dose-escalation group 1:ART002: 0.3mg/kg, single administration
Dose-escalation group 2:ART002: 0.75mg/kg, single administration
Dose-escalation group 3:ART002: 1.0mg/kg, single administration
Dose-escalation group 4:ART002: 1.25mg/kg, single administration
Sponsors
The First Affiliated Hospital of Bengbu Medical College
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Male or female, aged 18-70 years (inclusive) at the time of signing the informed consent form; 2. Weight between 45-90 kg (inclusive) at the time of screening; 3. Subjects who are receiving statin treatment or meet the indications for statin treatment at the time of screening, and the concomitant medication/treatment allowed has been stable for at least 4 weeks; 4. Confirmed diagnosis of HeFH, meeting any of the criteria 1) or 2): (1) Diagnosed with HeFH caused by LDLR, APOB or PCSK9 gene mutations; (2) Adults meet 2 of the following 3 items: 1). Untreated serum LDL-C >= 4.7 mmol/L; 2). Skin/tendon xanthomas or lipocalinous arcus (= 2.6 mmol/L (100 mg/dL); 6. Subjects must meet the following laboratory standards at screening: (1). Aspartate aminotransferase (AST), total bilirubin, international normalized ratio (INR) = 1.5 times the upper limit of normal (ULN); (2) . Alanine aminotransferase (ALT), alkaline phosphatase (ALP) or glutamyl transpeptidase (GGT) = 2 times the upper limit of normal (2×ULN); (3) . Platelet count >= 100,000 cells/mm3; (4) . Normal coagulation function; (5) . Fasting triglyceride <= 4.52mmol/L (= 400mg/dL); (6) . Lp(a) <= 500mg/L; 7. Must abstain from alcohol from the screening period to 28 days after medication; 8. Do not smoke and do not use nicotine for at least 90 days before screening; 9. For female subjects: should be surgically sterilized or postmenopausal subjects; For male subjects: should agree to take medically approved contraceptive measures (such as condom use, abstinence, etc.) during the study treatment and within 180 days after the study drug administration; 10. Able to understand this trial and have signed the informed consent form.
Exclusion criteria
Exclusion criteria: 1. Diagnosed with compound heterozygous FH, double heterozygous FH, homozygous FH (HoFH); 2. Subjects with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and peripheral blood HBV DNA titer >=1×10^2 copies/L; subjects with positive hepatitis C virus (HCV) antibody and positive peripheral blood HCV RNA; subjects with positive human immunodeficiency virus (HIV) antibody; 3. Any unstable systemic disease: including but not limited to unstable angina, cerebrovascular accident or transient ischemia (within 6 months before screening), myocardial infarction (within 6 months before screening), history of grade II-IV heart failure defined by the New York Heart Association (NYHA), severe arrhythmia requiring drug treatment, liver, kidney or metabolic diseases; 4. Patients with a history of percutaneous coronary artery balloon angioplasty (PTCA), percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), unstable angina within 90 days before randomization, or clear severe coronary artery stenosis supported by coronary CT or coronary angiography; 5. Active infection or uncontrollable infection requiring systemic treatment within 14 days before enrollment; 6. Subjects known to be allergic to any lipid nanoparticle (LNP) component; 7. New strenuous exercise started within 4 weeks before screening, or major changes in diet and lifestyle (exercise, smoking and drinking, etc.), or weight change >5kg; 8. Patients with a history of stroke or transient ischemic attack (TIA), or severe aortic or peripheral vascular disease, or indications for surgical intervention; 9. Uncontrolled hypertension, systolic blood pressure SBP =160mmHg and/or diastolic blood pressure DBP >=100mmHg at screening/baseline; 10. LDL-C >= 13mmol/L (500mg/dL); 11. Suffering from other diseases that may cause secondary increase in LDL-C or abnormal lipid levels; 12. Used Inclisirna, Toleximab, Recalcimab, Evolocumab, Alirocumab or other PCSK9 targeted drugs within 14 days or 5 half-lives (whichever is longer) before the first dose of the study drug; 13. Received LDL plasmapheresis treatment within the past 12 months; 14. Diagnosed with diabetes, glycosylated hemoglobin>8.5%; 15. History of cirrhosis; 16. Hospitalization or invasive surgery due to acute myocardial infarction, severe arrhythmia, severe hypertension, severe heart failure within 90 days before or during screening; 17. Unable or unwilling to accept the required pre-treatment drug treatment regimen; 18. Antiplatelet (such as aspirin, clopidogrel) or anticoagulant therapy (such as warfarin, dabigatran, apixaban) within 14 days before medication; 19. Liver, heart or other solid organ transplantation, bone marrow transplantation or planned transplantation within 1 year; 20. Patients who are judged by the investigator to be unsuitable for participation in the study due to other reasons (such as other concomitant diseases or medical history, alcohol dependence and/or drug abuse, subject compliance, etc.).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Hematology;Chemistry;Coagulation;Urinalysis;C-reactive protein;ComplementN (C3, C4);Cytokines (TNF-a, IL-6);Adverse event;Vital signs (including weight);Physical examination;Electrocardiogram; | — |
Secondary
| Measure | Time frame |
|---|---|
| Serum LDL-C;Serum PCSK9 protein;Pharmacokinetics (AUC0-28, AUClast,Cmax,Tmax, etc.); | — |
Countries
China
Contacts
Public ContactHuan Zhou/Ningru Zhang
The First Affiliated Hospital of Bengbu Medical College
Outcome results
None listed