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

Hypercholesterolemia, Familial Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03018678
• Other study ID #: 822899
• Status: Completed
• Start date: March 2016
• Est. completion date: December 3, 2019

Study information

• Verified date: March 2020
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: December 3, 2019
• Est. primary completion date: May 30, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypercholesterolemia
• Hypercholesterolemia, Familial
• Hyperlipoproteinemia Type II

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	genetic analysis	identification of genetic, confirmation of FH	Screening phase
Primary	Neutralizing antibodies	identification of subjects with no or minimal neutralizing antibodies titer <= 1:10	Screening phase