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

NCT ID: NCT03018678

Last Updated: 2020-03-06

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 21 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2019-12-03

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.

Conditions

Hypercholesterolemia, Familial

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients with HOFH

No intervention

No interventions assigned to this group

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marina Cuchel, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Associate Professor

Locations

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

822899

Identifier Type: -

Identifier Source: org_study_id