Safety and Efficacy Study of NGGT006 in Refractory Hypercholesterolemia Patients
This is an early phase 1, open-label, single-center, dose-escalation pilot trial to evaluate the safety and efficacy of an intravenous infusion of NGGT006 in patients with refractory Hypercholesterolemia diagnosed by gene testing for familial hypercholesterolemia. NGGT006 uses adeno-associated virus (AAV) as a vector, carrying a liver specific promoter and codon optimized human LDLR gene, driving the expression of LDLR protein with normal function and promoting the clearance of low-density lipoprotein cholesterol (LDL-C).
- EligibilityCriteria: Inclusion Criteria:  18 ≤ age ≤ 55 years old; A patient with a clear diagnosis of refractory hypercholesterolemia and confirmed by genetic testing to be familial hypercholesterolemia; AAV binding antibody titer ≤1:80 and AAV neutralizing antibody ≤1:5; 18≤BMI (body mass index)≤35;  During the screening period, the subjects have received stable maximum tolerated dose of lipid-lowering drug treatment, but LDL-C was still ≥70mg/dL with clinical atherosclerotic cardiovascular disease; or LDL-C level was ≥ 100 mg/dL without clinical atherosclerotic cardiovascular disease: the highest tolerated dose refers to (the following must be met at the same time):  ① Moderate to high doses of statins for ≥4 weeks, whether used alone or in combination with other lipid-lowering drugs; exceptions: subjects cannot tolerate statins; or subjects cannot receive statin treatment due to other reasons, such as low BMI, etc.;  ② Ezetimibe ≥ 4 weeks;  ③ Alirocumab 150mg Q2W or 300mg Q4W; evolocumab 140mg Q2W or 420mg Q4W; ≥8 weeks; And during the clinical trial process, any adjustment involving the type and dosage of lipid-lowering drugs must be approved by the researcher;  Stable healthy diet for ≥12 weeks, and can adhere to a healthy diet throughout the entire clinical trial; Voluntarily sign the informed consent form and be willing to comply with the trial visit plan; Willing to maintain a similar amount and intensity of exercise during the study period as during the baseline period; Maintain good living habits, have no history of alcoholism or alcohol dependence (ICD-10 diagnosis is F10) No new or recurring cardiovascular events (myocardial infarction, cerebral infarction, etc.) within half a year; No stent implantation plan within three months; Female subjects have not had sexual intercourse for 14 days before administration, and their blood tests indicate that they are not pregnant; Subjects of childbearing age agree to use highly effective contraceptive measures for at least 365 days from the time of NGGT006 administration.  Exclusion Criteria:  Secondary hyperlipidemia; Use of other drugs or nutritional products that may affect blood lipids (such as fibrates) within 6 weeks; Have received low-density lipoprotein apheresis (LDL apheresis) within the past 2 months; Large weight fluctuations (≥5kg) in the past 2 months; Positive for hepatitis B surface antigen, hepatitis C, human immunodeficiency virus (HIV)，syphilis test or other infections (such as Epstein-Barr virus, Mycoplasma pneumoniae, tuberculosis virus, HPV, Chlamydia pneumoniae, respiratory syncytial virus, Adenovirus and coxsackievirus group B, etc.); Clinically significant abnormalities in liver function test: alanine aminotransferase (ALT) >2 × upper limit of normal (ULN) and/or aspartate aminotransferase (AST) >2 × ULN; RR at the baseline >160/100mmHg (one repeated measurement is allowed); Uncontrollable myocardial infarction or heart failure, and those planning surgery within one year; or new acute coronary syndrome in the past six months; Diabetes diagnosed within 3 months or with poor control (HbA1c >9%); Abnormal thyroid function, or those using thyroid hormone replacement therapy but poorly controlled (TSH within the normal range for <12 weeks); Acute or chronic renal insufficiency; Hemoglobin (Hb) < 120g/L (male), Hb < 110 (female); Abnormal platelet counts or morphology; History or laboratory tests suggestive of thrombosis; Had contraindications to glucocorticoid (e.g., epilepsy, severe schizophrenia, active peptic ulcer)； Used systemic glucocorticoid treatment within 6 weeks before enrollment; Life expectancy less than 1 year; Suffering from malignant tumors such as liver cancer; liver fibrosis; Previous gene therapy treatment; Hypersensitivity to AAV preparations (for example trehalose) or cortisone or immunosuppressants (sirolimus, rituximab, tacrolimus); Suffering from immunodeficiency disease Participation in any other clinical trial within 3 months; Breastfeeding females; Any other condition that may not be appropriate for the study in the opinion of the Investigator. - HealthyVolunteers: No - Gender: All - MinimumAge: 18 Years - MaximumAge: 55 Years - StdAgeList: Adult