Homozygous Familial HypercholesterolemiaEarly Phase 1NCT06125847
NGGT006 Gene Therapy for Homozygous Familial Hypercholesterolemia
A Early Phase 1 study testing NGGT006 in people with Homozygous Familial Hypercholesterolemia, run by First Affiliated Hospital Xi'an Jiaotong University at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 12 to 55 years
- Conditions the study is for
- Homozygous Familial Hypercholesterolemia
- What is being tested?
- NGGT006
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteChina
- Study dates
- 29 Oct 2023to 30 Mar 2031
- Phase
- Early Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.;
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
First Affiliated Hospital of Xian Jiaotong University
Xi'an, Shaanxi, 710061
Tao Zheng, MD, 086-15229218127, zhengtao900305@163.com
Yue Wu, MD, 086-18092826334, yue.wu@xjtu.edu.cn
About this study
Official title: A Clinical Study for the Safety and Efficacy of Intravenous Infusion of NGGT006 in Treatment of Homozygous Familial Hypercholesterolemia With LDLR Mutations
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 the detailed description
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.
- Conditions
- Homozygous Familial Hypercholesterolemia
- Being tested
- NGGT006
- Keywords
- Homozygous familial hypercholesterolemia, Gene therapy, Low-density lipoprotein cholesterol
- Medical subject headings
- Homozygous Familial Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NGGT006Genetic
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).
| Study group | Role | What they receive |
|---|---|---|
| NGGT006 | Experimental | 4 doses of NGGT006 will be administered according to the principle of dose escalation Receives: Genetic: NGGT006 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-related adverse events (AE) and serious adverse events (SAE)
Incidence of AE and SAE, as assessed by physical examinations, clinical laboratory parameters and adverse event reporting
Measured: 52 weeks
Absolute change and percent change in LDL-C
Change in LDL-C concentration from baseline to week 52
Measured: 52 weeks
Secondary outcomes (5)
Absolute change and percent change in apoB
Change in lipid concentrations from baseline to week 52
Measured: 52 weeks
Absolute change and percent change in TC
Change in lipid concentrations from baseline to week 52
Measured: 52 weeks
Absolute change and percent change in HDL-C
Change in lipid concentrations from baseline to week 52
Measured: 52 weeks
Absolute change and percent change in TG
Change in lipid concentrations from baseline to week 52
Measured: 52 weeks
Absolute change and percent change in Lp(a)
Change in lipid concentrations from baseline to week 52
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2023
- Study start29 Oct 2023
- Primary completion30 Mar 2027 (estimated)
- Study completion30 Mar 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Homozygous Familial HypercholesterolemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital Xi'an Jiaotong University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Zuyi Yuan, M.D., Study chair, First Affiliated Hospital of Xian Jiaotong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06125847
- Sponsor's protocol ID
- NGGT006-P-2301
- Status last verified
- Sep 2026
- First submitted
- 30 Oct 2023
- Last updated
- 3 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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 42243546