A Clinical Study for the Safety and Efficacy of Intravenous Infusion of NGGT006 in Treatment of Refractory Hypercholesterolemia

NGGT006-P-2302

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).

2024-06-01

2025-03-31

2029-03-01

Not yet recruiting

Early phase I

9

Inclusion Criteria: 1. 18 ≤ age ≤ 55 years old; 2. A patient with a clear diagnosis of refractory hypercholesterolemia and confirmed by genetic testing to be familial hypercholesterolemia; 3. AAV binding antibody titer ≤1:80 and AAV neutralizing antibody ≤1:5; 4. 18≤BMI (body mass index)≤35; 5. 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; 6. Stable healthy diet for ≥12 weeks, and can adhere to a healthy diet throughout the entire clinical trial; 7. Voluntarily sign the informed consent form and be willing to comply with the trial visit plan; 8. Willing to maintain a similar amount and intensity of exercise during the study period as during the baseline period; 9. Maintain good living habits, have no history of alcoholism or alcohol dependence (ICD-10 diagnosis is F10) 10. No new or recurring cardiovascular events (myocardial infarction, cerebral infarction, etc.) within half a year; 11. No stent implantation plan within three months; 12. Female subjects have not had sexual intercourse for 14 days before administration, and their blood tests indicate that they are not pregnant; 13. Subjects of childbearing age agree to use highly effective contraceptive measures for at least 365 days from the time of NGGT006 administration. Exclusion Criteria: 1. Secondary hyperlipidemia; 2. Use of other drugs or nutritional products that may affect blood lipids (such as fibrates) within 6 weeks; 3. Have received low-density lipoprotein apheresis (LDL apheresis) within the past 2 months; 4. Large weight fluctuations (≥5kg) in the past 2 months; 5. 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.); 6. Clinically significant abnormalities in liver function test: alanine aminotransferase (ALT) \>2 × upper limit of normal (ULN) and/or aspartate aminotransferase (AST) \>2 × ULN; 7. RR at the baseline \>160/100mmHg (one repeated measurement is allowed); 8. Uncontrollable myocardial infarction or heart failure, and those planning surgery within one year; or new acute coronary syndrome in the past six months; 9. Diabetes diagnosed within 3 months or with poor control (HbA1c \>9%); 10. Abnormal thyroid function, or those using thyroid hormone replacement therapy but poorly controlled (TSH within the normal range for \<12 weeks); 11. Acute or chronic renal insufficiency; 12. Hemoglobin (Hb) \< 120g/L (male), Hb \< 110 (female); 13. Abnormal platelet counts or morphology; 14. History or laboratory tests suggestive of thrombosis; 15. Had contraindications to glucocorticoid (e.g., epilepsy, severe schizophrenia, active peptic ulcer)； 16. Used systemic glucocorticoid treatment within 6 weeks before enrollment; 17. Life expectancy less than 1 year; 18. Suffering from malignant tumors such as liver cancer; liver fibrosis; 19. Previous gene therapy treatment; 20. Hypersensitivity to AAV preparations (for example trehalose) or cortisone or immunosuppressants (sirolimus, rituximab, tacrolimus); 21. Suffering from immunodeficiency disease 22. Participation in any other clinical trial within 3 months; 23. Breastfeeding females; 24. Any other condition that may not be appropriate for the study in the opinion of the Investigator.

{'studyType': 'INTERVENTIONAL', 'phases': ['EARLY_PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 9, 'type': 'ESTIMATED'}}

2024-04-17