Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia

Study Overview
=================
Brief Summary
-----------------
The purpose of this protocol is to identify and screen potential candidates for future enrollment in a gene therapy clinical trial for HoFH.

Detailed Description
-----------------
Homozygous Familial Hypercholesterolemia (HoFH) is a rare genetic metabolic disorder characterized by markedly elevated LDL-cholesterol (LDL-C) levels, resulting in severe atherosclerosis often leading to early onset of cardiovascular disease. The most frequent cause is mutation in the LDL receptor gene (LDLR). LDL-C levels remain frequently above acceptable levels despite treatment with multiple existing lipid lowering drugs and/or LDL apheresis. 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. The purpose of this protocol is to identify and screen potential candidates for future enrollment in a gene therapy clinical trial. No study drug will be administered in this screening study.

Official Title
-----------------
Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia

Conditions
-----------------
Hypercholesterolemia, Familial

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males and females ≥ 18 years of age Clinical presentation consistent with homozygous FH Subjects must be able to comprehend and willing to provide a signed IRB approved Informed Consent Form Exclusion Criteria: Known to carry confirmed mutations in genes affecting LDL receptor functionality other than the LDLR gene History of cirrhosis based on documented histological evaluation or non-invasive imaging Documented diagnosis of any of the following liver diseases: Hepatitis B or C; Biopsy-proven nonalcoholic steatohepatitis; Biopsy-proven alcoholic liver disease; Autoimmune hepatitis; Primary biliary cirrhosis; Primary sclerosing cholangitis; Wilson's disease; Hemochromatosis; alpha1 anti-trypsin deficiency History of immunodeficiency diseases, including a positive HIV test result Previous organ transplantation Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study Inability to participate

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with HOFH<br>No intervention | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| genetic analysis | identification of genetic, confirmation of FH | Screening phase | 
| Neutralizing antibodies | identification of subjects with no or minimal neutralizing antibodies titer <= 1:10 | Screening phase |