Safety and Efficacy Study of NGGT006 in Refractory Hypercholesterolemia Patients

NCT06293729 | Not Yet Recruiting Early Phase 1

• 1 other identifier: NGGT006-P-2302
• Study Type: interventional
• Target: 9
• Locations: 0 countries
• Sites: N/A

Brief 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. 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).

Conditions

Refractory Hypercholesterolemia; Familial Hypercholesterolemia

Keywords

Gene therapy; Low-density lipoprotein cholesterol

Outcome Measures

Primary Outcomes (2)

• 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

  52 weeks

• Absolute change and percent change in LDL-C

  Change in LDL-C concentration from baseline to week 52

  52 weeks

Secondary Outcomes (8)

• Absolute change and percent change in non-high density lipoprotein cholesterol

  52 weeks

• Absolute change and percent change in apolipoprotein B

  52 weeks

• Absolute change and percent change in total cholesterol

  52 weeks

• Absolute change and percent change in HDL-C

  52 weeks

• Absolute change and percent change in triglycerides

  52 weeks

Study Arms (1)

NGGT006

EXPERIMENTAL

3 doses of NGGT006 will be administered according to the principle of dose escalation

Drug: NGGT006

Interventions

NGGT006 DRUG

Single intravenous infusion of NGGT006 at low dose (7.5e12vg/kg), medium dose (1.5e13vg/kg) and high dose (3e13vg/kg).

NGGT006

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• ≤ 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;
• ≤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;

You may not qualify if:

• 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)；

Sponsors & Collaborators

• Suzhou Municipal Hospital: lead

MeSH Terms

Conditions

Hypercholesterolemia; Hyperlipoproteinemia Type II

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias

Central Study Contacts

Jun Zhang, MD

CONTACT

+86 0512-62363323; zhangjun0808@njmu.edu.cn

Yan Chen, PhD

CONTACT

+86 0512-62363323; Chenyandoc@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: President of Suzhou Municipal Hospital

Study Record Dates

• First Submitted: February 27, 2024
• First Posted: March 5, 2024
• Study Start: June 1, 2024
• Primary Completion: March 31, 2025
• Study Completion (Estimated): March 1, 2029
• Last Updated: April 17, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share