NGGT006 Gene Therapy for Homozygous Familial Hypercholesterolemia
ID: NCT06125847
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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 homozygous familial hypercholesterolemia (HoFH) patients with LDLR mutations. NGGT006 is an adeno-associated viral (AAV) vector carrying 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).
Read Full Scientific Objectives & Methods
Homozygous familial hypercholesterolemia (HoFH) is a rare inherited disorder of lipoprotein metabolism, characterized by extreme elevations in low-density lipoprotein cholesterol (LDL-C) and leading to early onset of severe coronary artery disease. This is an early phase 1, open-label, single-center, dose-escalation, pilot trial to evaluate the safety and efficacy of a single intravenous infusion of NGGT006 in HoFH patients with LDLR mutations. NGGT006 is an adeno-associated viral (AAV) vector carrying 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). 4-21 subjects will be enrolled and divided into 4 groups according to the principle of dose escalation, respectively administered intravenous infusion of NGGT006 at dose group 1 (7.5e12vg/kg), dose group 2 (1.5e13vg/kg) , dose group 3 (3e13vg/kg) and dose group 4 (4e13vg/kg). The researcher is allowed to extend 0-9 patients. All subjects will undergo 52 weeks of treatment observation and further 260 weeks of long-term follow-up.
Single intravenous infusion of NGGT006 at dose 1 (7.5e12vg/kg), dose 2 (1.5e13vg/kg) , dose 3 (3e13vg/kg) and dose 4 (4e13vg/kg).
Treatment Arms Description
4 doses of NGGT006 will be administered according to the principle of dose escalation
- Voluntarily sign informed consent form;
- Male or female, 12 ≤ age ≤ 55 years (first patient≥ 18 years), diagnosed as homozygous familial hypercholesterolemia with genetic confirmation of two mutant alleles of the LDL receptor (LDLR) gene;
- AAV8 neutralizing antibodies can be negative or reduced to negative levels through methods such as plasma exchange or IgG-degrading enzymes.
- Untreated LDL-C ≥10 mmol/L (386mg/ dL) or treated LDL-C ≥7 mmol/L (270mg/ dL) together with cutaneous or tendon xanthoma before age 18 years;
- Had been on stable medication for ≥30 days if receiving lipid-lowering therapy (or ≥60 days if receiving alirocumab or evolocumab) prior to screening and not scheduled for addition of new drugs or dose adjustments during the study;
- Agreed to follow a low-fat diet and comply with all study procedures, including dietary requirements, study visits, fasting blood draws, and the study treatment regimen.;
- Agreed to maintain a similar exercise volume and intensity to baseline during the study period;
- Agreed to maintain good lifestyle habits;
- No history of alcohol abuse or alcohol dependence (diagnosed as F10 in ICD-10 code);
- No sexual activity for 14 days prior to administration and negative serum pregnancy test in female participants;
- Participants of childbearing potential agreed to use highly effective contraception for at least 365 days from administration of NGGT006;
- No plan of stent implantation within 3 months.
- Positive for hepatitis B surface antigen, hepatitis C, human immunodeficiency virus (HIV) or syphilis test;
- Clinically significant abnormalities in liver function test: alanine aminotransferase (ALT) \>3 × upper limit of normal (ULN) and/or aspartate aminotransferase (AST) \>3 × ULN;
- Baseline blood pressure \>160/100 mmHg (1 repeat measurement is allowed);
- Uncontrolled myocardial infarction or heart failure, or had surgery plan within 1 year;
- Diabetes diagnosed within 3 months or with poor control (HbA1c \>9%);
- Acute or chronic kidney failure;
- Hemoglobin (Hb) \<120g/L (male), Hb \<110 (female);
- Platelet test results deemed clinically significantly abnormal by the investigator;
- History or laboratory tests suggestive of thrombosis;
- Had contraindications to glucocorticoid (e.g., epilepsy, severe schizophrenia, active peptic ulcer);
- Life expectancy less than 1 year;
- With malignant tumors;
- Liver fibrosis or liver cancer;
- Previous gene therapy treatment;
- Hypersensitivity to any excipient of the AAV product (including trehalose) or cortisone or immunosuppressants (sirolimus, rituximab, tacrolimus);
- Participation in any other clinical trial within 3 months;
- History of stent implantation within 1 month or myocardial infarction within 3 months;
- Breastfeeding females;
- Any other condition that may not be appropriate for the study in the opinion of the Investigator.
Primary Outcome Measures
- Incidence of treatment-related adverse events (AE) and serious adverse events (SAE) — Time Frame: 52 weeks
Incidence of AE and SAE, as assessed by physical examinations, clinical laboratory parameters and adverse event reporting
- Absolute change and percent change in LDL-C — Time Frame: 52 weeks
Change in LDL-C concentration from baseline to week 52
View Secondary Outcome Measures (5)
- Absolute change and percent change in apoB — Time Frame: 52 weeks
Change in lipid concentrations from baseline to week 52
- Absolute change and percent change in TC — Time Frame: 52 weeks
Change in lipid concentrations from baseline to week 52
- Absolute change and percent change in HDL-C — Time Frame: 52 weeks
Change in lipid concentrations from baseline to week 52
- Absolute change and percent change in TG — Time Frame: 52 weeks
Change in lipid concentrations from baseline to week 52
- Absolute change and percent change in Lp(a) — Time Frame: 52 weeks
Change in lipid concentrations from baseline to week 52
This trial is recruiting at 1 study facilities worldwide. Click below to see if there is a clinic or hospital in your area:
Show All 1 Facilities & Contact Sites
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- Zheng T, Gao G, Xu C, Li R, Shao J, Wang X, Han X, Li J, Liu P, Xiong Y, Song L, Wang J, Wen S, Zhuo X, Wang G, Jiang L, Qu G, Chen T, She J, Luo Y, Yuan Z, Wu Y. AAV gene therapy for homozygous familial hypercholesterolemia: a phase 1 trial. Nat Med. 2026 Jun;32(6):2137-2146. doi: 10.1038/s41591-026-04441-3. Epub 2026 Jun 4.PubMed ↗
View Official Medical/Scientific Title
A Clinical Study for the Safety and Efficacy of Intravenous Infusion of NGGT006 in Treatment of Homozygous Familial Hypercholesterolemia With LDLR Mutations