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

University of Pennsylvania21 enrolled

Overview

The purpose of this protocol is to identify and screen potential candidates for future enrollment in a gene therapy clinical trial for HoFH.

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Hypercholesterolemia, Familial

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Outcomes

Primary Outcomes

genetic analysis

identification of genetic, confirmation of FH

Time frame: Screening phase

Neutralizing antibodies

identification of subjects with no or minimal neutralizing antibodies titer \<= 1:10

Time frame: Screening phase

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.