Refractory HypercholesterolemiaEarly Phase 1NCT06293729
Safety and Efficacy Study of NGGT006 in Refractory Hypercholesterolemia Patients
A Early Phase 1 study testing NGGT006 in people with Refractory Hypercholesterolemia and Familial Hypercholesterolemia, run by Suzhou Municipal Hospital.
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 patients with refractory Hypercholesterolemia diagnosed by gene testing for familial hypercholesterolemia. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Refractory Hypercholesterolemia, 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
- 9 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2024to 1 Mar 2029
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
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 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.;
Show all 16Show fewer
- 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.
Who cannot join
- 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;
Show all 24Show fewer
- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Clinical Study for the Safety and Efficacy of Intravenous Infusion of NGGT006 in Treatment of Refractory Hypercholesterolemia
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).
Read the detailed description
Familial Hypercholesterolemia caused by common genetic mutations can be divided into heterozygous hypercholesterolemia (HeFH, Heterozygous Familial Hypercholesterolemia) and homozygous hypercholesterolemia (HoFH, Homozygous Familial Hypercholesterolemia). Refractory hypercholesterolemia was defined as an LDL-C level of 70 mg/dL or greater, or 100 mg/dL or greater, for patients with or without clinical ASCVD, respectively. A large proportion of patients with familial hypercholesterolemia belong to refractory hypercholesterolemia. 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 patients with refractory Hypercholesterolemia diagnosed by gene testing for familial hypercholesterolemia. 3-9 subjects will be enrolled and divided into 3 groups according to the principle of dose escalation, respectively administered intravenous infusion of NGGT006 at low dose (7.5e12vg/kg), medium dose (1.5e13vg/kg) and high dose (3e13vg/kg). All subjects will undergo 52 weeks of treatment observation and further 260 weeks of long-term follow-up.
- Being tested
- NGGT006
- Keywords
- Gene therapy, Low-density lipoprotein cholesterol
- Medical subject headings
- Hypercholesterolemia, Hyperlipoproteinemia Type II
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NGGT006Drug
Single intravenous infusion of NGGT006 at low dose (7.5e12vg/kg), medium dose (1.5e13vg/kg) and high dose (3e13vg/kg).
| Study group | Role | What they receive |
|---|---|---|
| NGGT006 | Experimental | 3 doses of NGGT006 will be administered according to the principle of dose escalation Receives: Drug: 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 (8)
Absolute change and percent change in non-high density lipoprotein cholesterol
Change in non-HDL-C from baseline to week 52
Measured: 52 weeks
Absolute change and percent change in apolipoprotein B
Change in ApoB from baseline to week 52
Measured: 52 weeks
Absolute change and percent change in total cholesterol
Change in TC from baseline to week 52
Measured: 52 weeks
Absolute change and percent change in HDL-C
Change in HDL-C from baseline to week 52
Measured: 52 weeks
Absolute change and percent change in triglycerides
Change in TG from baseline to week 52
Measured: 52 weeks
Absolute change and percent change in very low-density lipoprotein cholesterol
Change in VLDL from baseline to week 52
Measured: 52 weeks
Absolute change and percent change in lipoprotein(a)
Change in Lp(a) from baseline to week 52
Measured: 52 weeks
Absolute change and percent change in apolipoprotein A-I
Change in apo A-I 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 posted5 Mar 2024
- Study start1 Jun 2024 (estimated)
- Primary completion31 Mar 2025 (estimated)
- Study completion1 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory 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
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Suzhou Municipal Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yan Chen, Suzhou Municipal Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06293729
- Sponsor's protocol ID
- NGGT006-P-2302
- Status last verified
- Apr 2024
- First submitted
- 27 Feb 2024
- Last updated
- 17 Apr 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Study for the Safety and Efficacy of Intravenous Infusion of NGGT006 in Treatment of Refractory Hypercholesterolemia
- ClinicalTrials.gov ID
- NCT06293729
- Acronym / sponsor ID
- NGGT006-P-2302
- Keywords
- Gene therapy, Low-density lipoprotein cholesterol
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 9 participants (estimated)
- Lead sponsor
- Suzhou Municipal HospitalUniversity, hospital or other
- Study start
- 1 Jun 2024 (estimated)
- Primary completion
- 31 Mar 2025 (estimated)
- Study completion
- 1 Mar 2029 (estimated)
- First posted
- 5 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Familial Hypercholesterolemia caused by common genetic mutations can be divided into heterozygous hypercholesterolemia (HeFH, Heterozygous Familial Hypercholesterolemia) and homozygous hypercholesterolemia (HoFH, Homozygous Familial Hypercholesterolemia). Refractory hypercholesterolemia was defined as an LDL-C level of 70 mg/dL or greater, or 100 mg/dL or greater, for patients with or without clinical ASCVD, respectively. A large proportion of patients with familial hypercholesterolemia belong to refractory hypercholesterolemia. 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 patients with refractory Hypercholesterolemia diagnosed by gene testing for familial hypercholesterolemia. 3-9 subjects will be enrolled and divided into 3 groups according to the principle of dose escalation, respectively administered intravenous infusion of NGGT006 at low dose (7.5e12vg/kg), medium dose (1.5e13vg/kg) and high dose (3e13vg/kg). All subjects will undergo 52 weeks of treatment observation and further 260 weeks of long-term follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NGGT006 | Experimental | Drug: NGGT0063 doses of NGGT006 will be administered according to the principle of dose escalation |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (16 listed)
- 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):
Key exclusion criteria (24 listed)
- 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.);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NGGT006Single intravenous infusion of NGGT006 at low dose (7.5e12vg/kg), medium dose (1.5e13vg/kg) and high dose (3e13vg/kg). | Drug | NGGT006 |
Primary outcome
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
8 secondary outcomes
Absolute change and percent change in non-high density lipoprotein cholesterol
Time frame: 52 weeks
Absolute change and percent change in apolipoprotein B
Time frame: 52 weeks
Absolute change and percent change in total cholesterol
Time frame: 52 weeks
Absolute change and percent change in HDL-C
Time frame: 52 weeks
Absolute change and percent change in triglycerides
Time frame: 52 weeks
Absolute change and percent change in very low-density lipoprotein cholesterol
Time frame: 52 weeks
Absolute change and percent change in lipoprotein(a)
Time frame: 52 weeks
Absolute change and percent change in apolipoprotein A-I
Time frame: 52 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2024.
- Individual participant dataSharing planned: No
Related trials for Refractory Hypercholesterolemia
RecruitingPhase 1
Phase 1b Study of VERVE-201 in Patients With Refractory Hyperlipidemia
Hypercholesterolemia, Hypertriglyceridemia
RecruitingPhase 1
A Safety and Tolerability Trial Evaluating CTX310 in Participants With Refractory Dyslipidemias
Cardiovascular, Metabolic Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing NGGT006 in people with Refractory Hypercholesterolemia and Familial Hypercholesterolemia, run by Suzhou Municipal Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 17 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jun Zhang, MD (+86 0512-62363323, zhangjun0808@njmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment-related adverse events (AE) and serious adverse events (SAE) (time frame: 52 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2024.