Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Hypercholesterolemia, Familial
- Sponsor
- University of Pennsylvania
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- Neutralizing antibodies
- Status
- Completed
- Last Updated
- 6 years ago
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.
Investigators
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
Outcomes
Primary Outcomes
Neutralizing antibodies
Time Frame: Screening phase
identification of subjects with no or minimal neutralizing antibodies titer \<= 1:10
genetic analysis
Time Frame: Screening phase
identification of genetic, confirmation of FH