NGGT006 Gene Therapy for Homozygous Familial Hypercholesterolemia

Launched by FIRST AFFILIATED HOSPITAL XI'AN JIAOTONG UNIVERSITY · Nov 5, 2023

Keywords

ClinConnect Summary

This clinical trial is investigating a new gene therapy called NGGT006, designed to help patients with a rare genetic condition known as homozygous familial hypercholesterolemia (HoFH). This condition causes dangerously high cholesterol levels due to mutations in the LDL receptor gene, which can lead to serious heart problems. The trial aims to see if NGGT006, which uses a specially modified virus to deliver a healthy version of the LDL receptor gene, can be safely infused into patients and effectively lower their cholesterol levels.

To participate in the trial, individuals must be between the ages of 12 and 55 and have been diagnosed with HoFH, confirmed by genetic testing. They should have very high cholesterol levels and must not have received certain treatments recently. Participants will need to follow specific guidelines, such as maintaining a low-fat diet and not taking new medications during the study. Throughout the trial, participants will be closely monitored for safety and effectiveness. This study is a promising step toward finding new treatments for those struggling with high cholesterol due to this genetic condition.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 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.
• • 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;
• • 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.
• Exclusion Criteria:
• • 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) ≥2 × upper limit of normal (ULN) and/or aspartate aminotransferase (AST) ≥2 × 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);
• • Abnormal platelet counts or morphology;
• • 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 AAV 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.