NGGT006 Gene Therapy for Homozygous Familial Hypercholesterolemia

NCT06125847 | Recruiting Early Phase 1 DMC

• 1 other identifier: NGGT006-P-2301
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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 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).

Conditions

Homozygous Familial Hypercholesterolemia

Keywords

Homozygous familial hypercholesterolemia; 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 (5)

• Absolute change and percent change in apoB

  52 weeks

• Absolute change and percent change in TC

  52 weeks

• Absolute change and percent change in HDL-C

  52 weeks

• Absolute change and percent change in TG

  52 weeks

• Absolute change and percent change in Lp(a)

  52 weeks

Study Arms (1)

NGGT006

EXPERIMENTAL

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

Genetic: NGGT006

Interventions

NGGT006 GENETIC

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).

NGGT006

Eligibility Criteria

• Age: 12 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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);

Sponsors & Collaborators

• First Affiliated Hospital Xi'an Jiaotong University: lead

Study Sites (1)

First Affiliated Hospital of Xian Jiaotong University

Xi'an, Shaanxi, 710061, China

RECRUITING

MeSH Terms

Conditions

Homozygous Familial Hypercholesterolemia

Condition Hierarchy (Ancestors)

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

Study Officials

• Zuyi Yuan, M.D.

  First Affiliated Hospital of Xian Jiaotong University

  STUDY CHAIR

Central Study Contacts

Tao Zheng, M.D.

CONTACT

086-15229218127; zhengtao900305@163.com

Ge Gao, M.M.

CONTACT

086-18229068097; gaoge1030@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2023
• First Posted: November 9, 2023
• Study Start: October 29, 2023
• Primary Completion: November 30, 2024
• Study Completion (Estimated): November 1, 2028
• Last Updated: December 9, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)