NCT02651675

A Gene Therapy Study for Homozygous Familial Hypercholesterolemia (HoFH)

AAV8-mediated Low Density Lipoprotein Receptor (LDLR) Gene Replacement in Subjects With Homozygous Familial Hypercholesterolemia (HoFH)

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 9 (actual)
• Sponsor: REGENXBIO Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This first-in-human study is intended to evaluate the safety and preliminary effectiveness of AAV (Adeno-associated virus)-based liver-directed gene therapy in the treatment of adults with Homozygous Familial Hypercholesterolemia (HoFH).

Detailed description

Homozygous Familial Hypercholesterolemia (HoFH) is a rare genetic metabolic disorder characterized by absent or severely reduced capacity to catabolize circulating LDL (Low density lipoprotein) particles by the hepatic LDL receptor. As a consequence, HoFH subjects present abnormal total plasma cholesterol (LDL-C) levels, resulting in severe atherosclerosis often leading to early onset of cardiovascular disease. Early initiation of aggressive treatment for these patients is therefore essential. Unfortunately, despite existing therapies, treated LDL-C (Low density lipoprotein cholesterol) levels could remain well above acceptable levels. Thus, the functional replacement of the defective LDLR via AAV-based liver-directed gene therapy may be a viable approach to treat this disease and improve response to current lipid-lowering treatments. This first-in-human study is intended to evaluate the safety of this gene therapy investigational product and assess preliminary evidence of efficacy using plasma LDL-C levels as a surrogate biomarker for human LDLR transgene expression. Subjects may be asked to participate in an optional kinetics study to assess the metabolic mechanism by which LDL-C is reduced.

Conditions

• Homozygous Familial Hypercholesterolemia (HoFH)

Interventions

Type	Name	Description
GENETIC	AAV directed hLDLR gene therapy	AAV directed hLDLR gene therapy is a novel adeno-associated viral (AAV8) vector with human low-density lipoprotein receptor (hLDLR) gene

Timeline

• Start date: 2016-03-01
• Primary completion: 2020-11-27
• Completion: 2020-11-27
• First posted: 2016-01-11
• Last updated: 2023-07-13
• Results posted: 2023-07-13

Locations

9 sites across 4 countries: United States, Canada, Italy, Netherlands

Regulatory

• FDA-regulated drug study